Trial Outcomes & Findings for Pharmacokinetic Drug-drug Interaction Study of Encorafenib and Binimetinib on Probe Drugs in Patients With BRAF V600-mutant Melanoma or Other Advanced Solid Tumors (NCT NCT03864042)
NCT ID: NCT03864042
Last Updated: 2024-09-27
Results Overview
Cmax is the maximum plasma concentration which was observed directly from the concentration-time data.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
56 participants
Primary outcome timeframe
Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
Results posted on
2024-09-27
Participant Flow
This study was conducted in 3 Arms to evaluate the potential drug-drug interactions (DDIs) of single and multiple oral doses of encorafenib in combination with binimetinib with sensitive substrates of specific cytochrome P450 (CYP) enzymes (Arm 1), organic anion-transporting polypeptide (OATP)/breast cancer resistance protein (BCRP) transporters (Arm 2), and moderate CYP3A4 inducer (Arm 3). A total of 29, 12, 15 participants were enrolled in Arm 1, Arm 2, and Arm 3, respectively.
Participant milestones
| Measure |
Arm 1 - CYP Probe Cocktail
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 milligrams \[mg\], dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg once daily \[QD\]) and binimetinib (tablet, 45 mg twice daily \[BID\]) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion immediate release (IR) tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
DDI Phase
STARTED
|
29
|
12
|
15
|
|
DDI Phase
COMPLETED
|
25
|
12
|
15
|
|
DDI Phase
NOT COMPLETED
|
4
|
0
|
0
|
|
Post-DDI Phase
STARTED
|
25
|
12
|
15
|
|
Post-DDI Phase
COMPLETED
|
0
|
0
|
0
|
|
Post-DDI Phase
NOT COMPLETED
|
25
|
12
|
15
|
Reasons for withdrawal
| Measure |
Arm 1 - CYP Probe Cocktail
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 milligrams \[mg\], dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg once daily \[QD\]) and binimetinib (tablet, 45 mg twice daily \[BID\]) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion immediate release (IR) tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
DDI Phase
Adverse Event
|
2
|
0
|
0
|
|
DDI Phase
Physician Decision
|
1
|
0
|
0
|
|
DDI Phase
Progressive Disease
|
1
|
0
|
0
|
|
Post-DDI Phase
Adverse Event
|
5
|
3
|
2
|
|
Post-DDI Phase
Progressive Disease
|
11
|
6
|
13
|
|
Post-DDI Phase
Discretion of investigator
|
1
|
1
|
0
|
|
Post-DDI Phase
Study terminated by sponsor
|
7
|
0
|
0
|
|
Post-DDI Phase
Withdrawal of consent
|
1
|
2
|
0
|
Baseline Characteristics
Pharmacokinetic Drug-drug Interaction Study of Encorafenib and Binimetinib on Probe Drugs in Patients With BRAF V600-mutant Melanoma or Other Advanced Solid Tumors
Baseline characteristics by cohort
| Measure |
Arm 1 - CYP Probe Cocktail
n=27 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
n=12 Participants
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil
n=15 Participants
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met.continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
Total
n=54 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
62.3 Years
STANDARD_DEVIATION 12.14 • n=99 Participants
|
61.3 Years
STANDARD_DEVIATION 13.65 • n=107 Participants
|
58.9 Years
STANDARD_DEVIATION 9.98 • n=206 Participants
|
61.1 Years
STANDARD_DEVIATION 11.9 • n=7 Participants
|
|
Sex: Female, Male
Female
|
14 Participants
n=99 Participants
|
6 Participants
n=107 Participants
|
7 Participants
n=206 Participants
|
27 Participants
n=7 Participants
|
|
Sex: Female, Male
Male
|
13 Participants
n=99 Participants
|
6 Participants
n=107 Participants
|
8 Participants
n=206 Participants
|
27 Participants
n=7 Participants
|
|
Race/Ethnicity, Customized
White
|
25 Participants
n=99 Participants
|
11 Participants
n=107 Participants
|
14 Participants
n=206 Participants
|
50 Participants
n=7 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
1 Participants
n=7 Participants
|
|
Race/Ethnicity, Customized
Asian
|
0 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
2 Participants
n=7 Participants
|
|
Race/Ethnicity, Customized
Other
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
1 Participants
n=7 Participants
|
PRIMARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline pharmacokinetic (PK) sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
Cmax is the maximum plasma concentration which was observed directly from the concentration-time data.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Maximum Concentration (Cmax) of Plasma Midazolam on Day -7, Day 1, and Day 14
Day -7
|
9.45 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 45.1
|
—
|
—
|
|
Maximum Concentration (Cmax) of Plasma Midazolam on Day -7, Day 1, and Day 14
Day 1
|
11.1 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 50.6
|
—
|
—
|
|
Maximum Concentration (Cmax) of Plasma Midazolam on Day -7, Day 1, and Day 14
Day 14
|
2.44 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 54.6
|
—
|
—
|
PRIMARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
Cmax is the maximum plasma concentration which was observed directly from the concentration-time data. The metabolites of midazolam included total 1-OH midazolam, free 1-OH midazolam, and glucuronide conjugated 1-hydroxymidazolam.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Cmax of Plasma Total 1-OH Midazolam on Day -7, Day 1, and Day 14
Day 14
|
56.7 ng/mL
Geometric Coefficient of Variation 27.7
|
—
|
—
|
|
Cmax of Plasma Total 1-OH Midazolam on Day -7, Day 1, and Day 14
Day -7
|
45.2 ng/mL
Geometric Coefficient of Variation 31.5
|
—
|
—
|
|
Cmax of Plasma Total 1-OH Midazolam on Day -7, Day 1, and Day 14
Day 1
|
50.5 ng/mL
Geometric Coefficient of Variation 40.8
|
—
|
—
|
PRIMARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
Cmax is the maximum plasma concentration which was observed directly from the concentration-time data. The metabolites of midazolam included total 1-OH midazolam, free 1-OH midazolam, and glucuronide conjugated 1-hydroxymidazolam.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Cmax of Plasma Free 1-OH Midazolam on Day -7, Day 1, and Day 14
Day -7
|
3.36 ng/mL
Geometric Coefficient of Variation 53.4
|
—
|
—
|
|
Cmax of Plasma Free 1-OH Midazolam on Day -7, Day 1, and Day 14
Day 1
|
4.52 ng/mL
Geometric Coefficient of Variation 52.7
|
—
|
—
|
|
Cmax of Plasma Free 1-OH Midazolam on Day -7, Day 1, and Day 14
Day 14
|
2.09 ng/mL
Geometric Coefficient of Variation 71.6
|
—
|
—
|
PRIMARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
Cmax is the maximum plasma concentration which was observed directly from the concentration-time data. The metabolites of midazolam included total 1-OH midazolam, free 1-OH midazolam, and glucuronide conjugated 1-hydroxymidazolam.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Cmax of Plasma Glucuronide Conjugated 1-Hydroxymidazolam on Day -7, Day 1, and Day 14
Day -7
|
41.5 ng/mL
Geometric Coefficient of Variation 32.8
|
—
|
—
|
|
Cmax of Plasma Glucuronide Conjugated 1-Hydroxymidazolam on Day -7, Day 1, and Day 14
Day 1
|
45.4 ng/mL
Geometric Coefficient of Variation 43.7
|
—
|
—
|
|
Cmax of Plasma Glucuronide Conjugated 1-Hydroxymidazolam on Day -7, Day 1, and Day 14
Day 14
|
54.1 ng/mL
Geometric Coefficient of Variation 29.1
|
—
|
—
|
PRIMARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
Cmax is the maximum plasma concentration which was observed directly from the concentration-time data. Due to dietary caffeine intake may resulted in positive pre-dose concentrations, absolute and/or baseline-adjusted caffeine were analyzed. Baseline adjusted concentration = measured concentration - \[predose concentration\*e\^(-Kel\*t)\], where Kel is terminal elimination rate constant based on actual measured concentration values for each profile and t is the actual sampling time.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Cmax of Plasma Absolute Caffeine on Day -7, Day 1, and Day 14
Day -7
|
1150 ng/mL
Geometric Coefficient of Variation 31.5
|
—
|
—
|
|
Cmax of Plasma Absolute Caffeine on Day -7, Day 1, and Day 14
Day 1
|
1210 ng/mL
Geometric Coefficient of Variation 30.6
|
—
|
—
|
|
Cmax of Plasma Absolute Caffeine on Day -7, Day 1, and Day 14
Day 14
|
1300 ng/mL
Geometric Coefficient of Variation 19.8
|
—
|
—
|
PRIMARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
Cmax is the maximum plasma concentration which was observed directly from the concentration-time data. Due to dietary caffeine intake may resulted in positive pre-dose concentrations, absolute and/or baseline-adjusted caffeine were analyzed. Baseline adjusted concentration = measured concentration - \[predose concentration\*e\^(-Kel\*t)\], where Kel is terminal elimination rate constant based on actual measured concentration values for each profile and t is the actual sampling time.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Cmax of Plasma Baseline-Adjusted Caffeine on Day -7, Day 1, and Day 14
Day -7
|
984 ng/mL
Geometric Coefficient of Variation 37.2
|
—
|
—
|
|
Cmax of Plasma Baseline-Adjusted Caffeine on Day -7, Day 1, and Day 14
Day 1
|
1070 ng/mL
Geometric Coefficient of Variation 40.4
|
—
|
—
|
|
Cmax of Plasma Baseline-Adjusted Caffeine on Day -7, Day 1, and Day 14
Day 14
|
1110 ng/mL
Geometric Coefficient of Variation 29.7
|
—
|
—
|
PRIMARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
Cmax is the maximum plasma concentration which was observed directly from the concentration-time data. Paraxanthine was the metabolite of caffeine.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Cmax of Plasma Paraxanthine on Day -7, Day 1, and Day 14
Day -7
|
357 ng/mL
Geometric Coefficient of Variation 41.6
|
—
|
—
|
|
Cmax of Plasma Paraxanthine on Day -7, Day 1, and Day 14
Day 1
|
319 ng/mL
Geometric Coefficient of Variation 27.7
|
—
|
—
|
|
Cmax of Plasma Paraxanthine on Day -7, Day 1, and Day 14
Day 14
|
247 ng/mL
Geometric Coefficient of Variation 53.5
|
—
|
—
|
PRIMARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
Cmax is the maximum plasma concentration which was observed directly from the concentration-time data.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Cmax of Plasma Omeprazole on Day -7, Day 1, and Day 14
Day -7
|
267 ng/mL
Geometric Coefficient of Variation 188.7
|
—
|
—
|
|
Cmax of Plasma Omeprazole on Day -7, Day 1, and Day 14
Day 1
|
354 ng/mL
Geometric Coefficient of Variation 73.1
|
—
|
—
|
|
Cmax of Plasma Omeprazole on Day -7, Day 1, and Day 14
Day 14
|
271 ng/mL
Geometric Coefficient of Variation 57.1
|
—
|
—
|
PRIMARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
Cmax is the maximum plasma concentration which was observed directly from the concentration-time data. 5-OH Omeprazole was the metabolite of omeprazole.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Cmax of Plasma 5-OH Omeprazole on Day -7, Day 1, and Day 14
Day -7
|
91.8 ng/mL
Geometric Coefficient of Variation 104.5
|
—
|
—
|
|
Cmax of Plasma 5-OH Omeprazole on Day -7, Day 1, and Day 14
Day 1
|
90.4 ng/mL
Geometric Coefficient of Variation 79.3
|
—
|
—
|
|
Cmax of Plasma 5-OH Omeprazole on Day -7, Day 1, and Day 14
Day 14
|
64.4 ng/mL
Geometric Coefficient of Variation 54.8
|
—
|
—
|
PRIMARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 2 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 2 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
Cmax is the maximum plasma concentration which was observed directly from the concentration-time data.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=10 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Cmax of Plasma Rosuvastatin on Day -7, Day 1 and Day 14
Day -7
|
6.98 ng/mL
Geometric Coefficient of Variation 96.4
|
—
|
—
|
|
Cmax of Plasma Rosuvastatin on Day -7, Day 1 and Day 14
Day 1
|
30.3 ng/mL
Geometric Coefficient of Variation 130.8
|
—
|
—
|
|
Cmax of Plasma Rosuvastatin on Day -7, Day 1 and Day 14
Day 14
|
18.7 ng/mL
Geometric Coefficient of Variation 113.7
|
—
|
—
|
PRIMARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 2 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 2 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
Cmax is the maximum plasma concentration which was observed directly from the concentration-time data.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=10 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Cmax of Plasma Bupropion on Day -7, Day 1 and Day 14
Day -7
|
94.0 ng/mL
Geometric Coefficient of Variation 63.9
|
—
|
—
|
|
Cmax of Plasma Bupropion on Day -7, Day 1 and Day 14
Day 1
|
70.9 ng/mL
Geometric Coefficient of Variation 50.6
|
—
|
—
|
|
Cmax of Plasma Bupropion on Day -7, Day 1 and Day 14
Day 14
|
71.0 ng/mL
Geometric Coefficient of Variation 52.7
|
—
|
—
|
PRIMARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 2 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 2 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
Cmax is the maximum plasma concentration which was observed directly from the concentration-time data. Hydroxybupropion was the metabolite of bupropion.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=10 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Cmax of Plasma Hydroxybupropion on Day -7, Day 1 and Day 14
Day -7
|
181 ng/mL
Geometric Coefficient of Variation 46.9
|
—
|
—
|
|
Cmax of Plasma Hydroxybupropion on Day -7, Day 1 and Day 14
Day 1
|
189 ng/mL
Geometric Coefficient of Variation 49.7
|
—
|
—
|
|
Cmax of Plasma Hydroxybupropion on Day -7, Day 1 and Day 14
Day 14
|
256 ng/mL
Geometric Coefficient of Variation 62.5
|
—
|
—
|
PRIMARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
AUClast is area under the concentration-time profile (AUC) from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Area Under the Concentration-Time Profile From Time 0 to The Time of The Last Quantifiable Concentration (AUClast) of Plasma Midazolam on Day -7, Day 1, and Day 14
Day -7
|
25.7 nanograms*hour per milliliter (ng*hr/mL)
Geometric Coefficient of Variation 57.2
|
—
|
—
|
|
Area Under the Concentration-Time Profile From Time 0 to The Time of The Last Quantifiable Concentration (AUClast) of Plasma Midazolam on Day -7, Day 1, and Day 14
Day 1
|
27.6 nanograms*hour per milliliter (ng*hr/mL)
Geometric Coefficient of Variation 58.4
|
—
|
—
|
|
Area Under the Concentration-Time Profile From Time 0 to The Time of The Last Quantifiable Concentration (AUClast) of Plasma Midazolam on Day -7, Day 1, and Day 14
Day 14
|
4.52 nanograms*hour per milliliter (ng*hr/mL)
Geometric Coefficient of Variation 52.9
|
—
|
—
|
PRIMARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
AUClast is AUC from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method. The metabolites of midazolam included total 1-OH midazolam, free 1-OH midazolam, and glucuronide conjugated 1-hydroxymidazolam.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
AUClast of Plasma Total 1-OH Midazolam on Day -7, Day 1, and Day 14
Day -7
|
135 ng*hr/mL
Geometric Coefficient of Variation 29.9
|
—
|
—
|
|
AUClast of Plasma Total 1-OH Midazolam on Day -7, Day 1, and Day 14
Day 1
|
173 ng*hr/mL
Geometric Coefficient of Variation 41.8
|
—
|
—
|
|
AUClast of Plasma Total 1-OH Midazolam on Day -7, Day 1, and Day 14
Day 14
|
142 ng*hr/mL
Geometric Coefficient of Variation 38.9
|
—
|
—
|
PRIMARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
AUClast is AUC from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method. The metabolites of midazolam included total 1-OH midazolam, free 1-OH midazolam, and glucuronide conjugated 1-hydroxymidazolam.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
AUClast of Plasma Free 1-OH Midazolam on Day -7, Day 1, and Day 14
Day -7
|
8.87 ng*hr/mL
Geometric Coefficient of Variation 43.7
|
—
|
—
|
|
AUClast of Plasma Free 1-OH Midazolam on Day -7, Day 1, and Day 14
Day 1
|
11.1 ng*hr/mL
Geometric Coefficient of Variation 46.6
|
—
|
—
|
|
AUClast of Plasma Free 1-OH Midazolam on Day -7, Day 1, and Day 14
Day 14
|
4.55 ng*hr/mL
Geometric Coefficient of Variation 62.6
|
—
|
—
|
PRIMARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
AUClast is AUC from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method. The metabolites of midazolam included total 1-OH midazolam, free 1-OH midazolam, and glucuronide conjugated 1-hydroxymidazolam.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
AUClast of Plasma Glucuronide Conjugated 1-Hydroxymidazolam on Day -7, Day 1, and Day 14
Day -7
|
125 ng*hr/mL
Geometric Coefficient of Variation 32.0
|
—
|
—
|
|
AUClast of Plasma Glucuronide Conjugated 1-Hydroxymidazolam on Day -7, Day 1, and Day 14
Day 1
|
160 ng*hr/mL
Geometric Coefficient of Variation 44.5
|
—
|
—
|
|
AUClast of Plasma Glucuronide Conjugated 1-Hydroxymidazolam on Day -7, Day 1, and Day 14
Day 14
|
133 ng*hr/mL
Geometric Coefficient of Variation 41.0
|
—
|
—
|
PRIMARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
AUClast is AUC from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method. Due to dietary caffeine intake may resulted in positive pre-dose concentrations, absolute and/or baseline-adjusted caffeine were analyzed. Baseline adjusted concentration = measured concentration - \[predose concentration\*e\^(-Kel\*t)\], where Kel is terminal elimination rate constant based on actual measured concentration values for each profile and t is the actual sampling time.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
AUClast of Plasma Absolute Caffeine on Day -7, Day 1, and Day 14
Day -7
|
5940 ng*hr/mL
Geometric Coefficient of Variation 35.8
|
—
|
—
|
|
AUClast of Plasma Absolute Caffeine on Day -7, Day 1, and Day 14
Day 1
|
6480 ng*hr/mL
Geometric Coefficient of Variation 34.4
|
—
|
—
|
|
AUClast of Plasma Absolute Caffeine on Day -7, Day 1, and Day 14
Day 14
|
7520 ng*hr/mL
Geometric Coefficient of Variation 22.7
|
—
|
—
|
PRIMARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
AUClast is AUC from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method. Due to dietary caffeine intake may resulted in positive pre-dose concentrations, absolute and/or baseline-adjusted caffeine were analyzed. Baseline adjusted concentration = measured concentration - \[predose concentration\*e\^(-Kel\*t)\], where Kel is terminal elimination rate constant based on actual measured concentration values for each profile and t is the actual sampling time.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
AUClast of Plasma Baseline-Adjusted Caffeine on Day -7, Day 1, and Day 14
Day -7
|
5100 ng*hr/mL
Geometric Coefficient of Variation 36.6
|
—
|
—
|
|
AUClast of Plasma Baseline-Adjusted Caffeine on Day -7, Day 1, and Day 14
Day 1
|
5700 ng*hr/mL
Geometric Coefficient of Variation 45.7
|
—
|
—
|
|
AUClast of Plasma Baseline-Adjusted Caffeine on Day -7, Day 1, and Day 14
Day 14
|
6430 ng*hr/mL
Geometric Coefficient of Variation 29.6
|
—
|
—
|
PRIMARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
AUClast is AUC from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method. Paraxanthine was the metabolite of caffeine.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
AUClast of Plasma Paraxanthine on Day -7, Day 1, and Day 14
Day -7
|
2160 ng*hr/mL
Geometric Coefficient of Variation 47.7
|
—
|
—
|
|
AUClast of Plasma Paraxanthine on Day -7, Day 1, and Day 14
Day 1
|
1940 ng*hr/mL
Geometric Coefficient of Variation 31.5
|
—
|
—
|
|
AUClast of Plasma Paraxanthine on Day -7, Day 1, and Day 14
Day 14
|
1470 ng*hr/mL
Geometric Coefficient of Variation 64.6
|
—
|
—
|
PRIMARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
AUClast is AUC from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
AUClast of Plasma Omeprazole on Day -7, Day 1, and Day 14
Day -7
|
815 ng*hr/mL
Geometric Coefficient of Variation 193.3
|
—
|
—
|
|
AUClast of Plasma Omeprazole on Day -7, Day 1, and Day 14
Day 1
|
1020 ng*hr/mL
Geometric Coefficient of Variation 91.9
|
—
|
—
|
|
AUClast of Plasma Omeprazole on Day -7, Day 1, and Day 14
Day 14
|
674 ng*hr/mL
Geometric Coefficient of Variation 54.3
|
—
|
—
|
PRIMARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
AUClast is AUC from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method. 5-OH Omeprazole was the metabolite of omeprazole.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
AUClast of Plasma 5-OH Omeprazole in Arm 1 on Day -7, Day 1 and Day 14
Day -7
|
313 ng*hr/mL
Geometric Coefficient of Variation 134.6
|
—
|
—
|
|
AUClast of Plasma 5-OH Omeprazole in Arm 1 on Day -7, Day 1 and Day 14
Day 1
|
302 ng*hr/mL
Geometric Coefficient of Variation 92.1
|
—
|
—
|
|
AUClast of Plasma 5-OH Omeprazole in Arm 1 on Day -7, Day 1 and Day 14
Day 14
|
195 ng*hr/mL
Geometric Coefficient of Variation 60.6
|
—
|
—
|
PRIMARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 2 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 2 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
AUClast is AUC from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=10 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
AUClast of Plasma Rosuvastatin on Day -7, Day 1 and Day 14
Day -7
|
33.6 ng*hr/mL
Geometric Coefficient of Variation 88.1
|
—
|
—
|
|
AUClast of Plasma Rosuvastatin on Day -7, Day 1 and Day 14
Day 1
|
93.8 ng*hr/mL
Geometric Coefficient of Variation 97.9
|
—
|
—
|
|
AUClast of Plasma Rosuvastatin on Day -7, Day 1 and Day 14
Day 14
|
52.8 ng*hr/mL
Geometric Coefficient of Variation 66.3
|
—
|
—
|
PRIMARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 2 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 2 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
AUClast is AUC from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=10 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
AUClast of Plasma Bupropion on Day -7, Day 1 and Day 14
Day -7
|
339 ng*hr/mL
Geometric Coefficient of Variation 48.1
|
—
|
—
|
|
AUClast of Plasma Bupropion on Day -7, Day 1 and Day 14
Day 1
|
261 ng*hr/mL
Geometric Coefficient of Variation 49.0
|
—
|
—
|
|
AUClast of Plasma Bupropion on Day -7, Day 1 and Day 14
Day 14
|
250 ng*hr/mL
Geometric Coefficient of Variation 50.1
|
—
|
—
|
PRIMARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 2 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 2 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
AUClast is AUC from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method. Hydroxybupropion was the metabolite of bupropion.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=10 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
AUClast of Plasma Hydroxybupropion on Day -7, Day 1 and Day 14
Day -7
|
1090 ng*hr/mL
Geometric Coefficient of Variation 59.8
|
—
|
—
|
|
AUClast of Plasma Hydroxybupropion on Day -7, Day 1 and Day 14
Day 1
|
1080 ng*hr/mL
Geometric Coefficient of Variation 63.8
|
—
|
—
|
|
AUClast of Plasma Hydroxybupropion on Day -7, Day 1 and Day 14
Day 14
|
1610 ng*hr/mL
Geometric Coefficient of Variation 65.7
|
—
|
—
|
PRIMARY outcome
Timeframe: 0 to 8 hours after dosing on Days -7, 1 and 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
Ae0-8 is the amount excreted into the urine over the collection interval of 0 to 8 hours.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
The Amount Eliminated Via Urine Over an 8-Hour Period (Ae0-8) of Losartan on Day -7, Day 1 and Day 14
Day -7
|
0.239 milligrams (mg)
Geometric Coefficient of Variation 268.0
|
—
|
—
|
|
The Amount Eliminated Via Urine Over an 8-Hour Period (Ae0-8) of Losartan on Day -7, Day 1 and Day 14
Day 1
|
0.349 milligrams (mg)
Geometric Coefficient of Variation 314.2
|
—
|
—
|
|
The Amount Eliminated Via Urine Over an 8-Hour Period (Ae0-8) of Losartan on Day -7, Day 1 and Day 14
Day 14
|
0.286 milligrams (mg)
Geometric Coefficient of Variation 277.3
|
—
|
—
|
PRIMARY outcome
Timeframe: 0 to 8 hours after dosing on Days -7, 1 and 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
Ae0-8 is the amount excreted into the urine over the collection interval of 0 to 8 hours. E-3174 was the metabolite of losartan.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Ae0-8 of E-3174 on Day -7, Day 1 and Day 14
Day -7
|
0.227 mg
Geometric Coefficient of Variation 293.3
|
—
|
—
|
|
Ae0-8 of E-3174 on Day -7, Day 1 and Day 14
Day 1
|
0.332 mg
Geometric Coefficient of Variation 276.2
|
—
|
—
|
|
Ae0-8 of E-3174 on Day -7, Day 1 and Day 14
Day 14
|
0.205 mg
Geometric Coefficient of Variation 317.8
|
—
|
—
|
PRIMARY outcome
Timeframe: 0 to 8 hours after dosing on Days -7, 1 and 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
Ae0-8 is the amount excreted into the urine over the collection interval of 0 to 8 hours.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Ae0-8 of Dextromethorphan on Day -7, Day 1 and Day 14
Day -7
|
0.0264 mg
Geometric Coefficient of Variation 396.7
|
—
|
—
|
|
Ae0-8 of Dextromethorphan on Day -7, Day 1 and Day 14
Day 1
|
0.0323 mg
Geometric Coefficient of Variation 542.5
|
—
|
—
|
|
Ae0-8 of Dextromethorphan on Day -7, Day 1 and Day 14
Day 14
|
0.0225 mg
Geometric Coefficient of Variation 899.2
|
—
|
—
|
PRIMARY outcome
Timeframe: 0 to 8 hours after dosing on Days -7, 1 and 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
Ae0-8 is the amount excreted into the urine over the collection interval of 0 to 8 hours. Dextrorphan was the metabolite of dextromethorphan.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Ae0-8 of Dextrorphan on Day -7, Day 1 and Day 14
Day -7
|
3.78 mg
Geometric Coefficient of Variation 183.9
|
—
|
—
|
|
Ae0-8 of Dextrorphan on Day -7, Day 1 and Day 14
Day 1
|
4.41 mg
Geometric Coefficient of Variation 165.5
|
—
|
—
|
|
Ae0-8 of Dextrorphan on Day -7, Day 1 and Day 14
Day 14
|
3.55 mg
Geometric Coefficient of Variation 222.5
|
—
|
—
|
PRIMARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21Population: All participants in Arm 3 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days 14 and 21. Number of participants analyzed represents the total number of participants in Arm 3 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
Cmax is the maximum plasma concentration which was observed directly from the concentration-time data.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=11 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Cmax of Plasma Encorafenib on Day 14 and Day 21 in Arm 3
Day 14
|
3540 ng/mL
Geometric Coefficient of Variation 55.6
|
—
|
—
|
|
Cmax of Plasma Encorafenib on Day 14 and Day 21 in Arm 3
Day 21
|
2830 ng/mL
Geometric Coefficient of Variation 67.2
|
—
|
—
|
PRIMARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21Population: All participants in Arm 3 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days 14 and 21. Number of participants analyzed represents the total number of participants in Arm 3 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
Cmax is the maximum plasma concentration which was observed directly from the concentration-time data. LHY746 was the metabolite of encorafenib.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=11 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Cmax of Plasma LHY746 on Day 14 and Day 21 in Arm 3
Day 14
|
2460 ng/mL
Geometric Coefficient of Variation 24.7
|
—
|
—
|
|
Cmax of Plasma LHY746 on Day 14 and Day 21 in Arm 3
Day 21
|
2510 ng/mL
Geometric Coefficient of Variation 26.8
|
—
|
—
|
PRIMARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21Population: All participants in Arm 3 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days 14 and 21. Number of participants analyzed represents the total number of participants in Arm 3 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
AUClast is AUC from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=11 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
AUClast of Plasma Encorafenib on Day 14 and Day 21 in Arm 3
Day 14
|
11900 ng*hr/mL
Geometric Coefficient of Variation 35.8
|
—
|
—
|
|
AUClast of Plasma Encorafenib on Day 14 and Day 21 in Arm 3
Day 21
|
9100 ng*hr/mL
Geometric Coefficient of Variation 30.3
|
—
|
—
|
PRIMARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21Population: All participants in Arm 3 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days 14 and 21. Number of participants analyzed represents the total number of participants in Arm 3 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
AUClast is AUC from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method. LHY746 was the metabolite of encorafenib.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=11 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
AUClast of Plasma LHY746 on Day 14 and Day 21 in Arm 3
Day 14
|
31100 ng*hr/mL
Geometric Coefficient of Variation 45.4
|
—
|
—
|
|
AUClast of Plasma LHY746 on Day 14 and Day 21 in Arm 3
Day 21
|
33100 ng*hr/mL
Geometric Coefficient of Variation 31.2
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
MRAUClast is the ratio of AUClast values of the metabolite compared to parent, corrected for molecular weight (MW), which was calculated by \[AUClast (metabolite) × MW (parent)\] / \[AUClast (parent) × MW (metabolite)\]. 1-OH midazolam was the metabolite of midazolam.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Ratio of AUClast Values of the Metabolite Compared to Parent (MRAUClast) for 1-OH Midazolam/Midazolam on Day -7, Day 1 and Day 14
Day -7
|
5.00 Ratio
Geometric Coefficient of Variation 63.3
|
—
|
—
|
|
Ratio of AUClast Values of the Metabolite Compared to Parent (MRAUClast) for 1-OH Midazolam/Midazolam on Day -7, Day 1 and Day 14
Day 1
|
5.97 Ratio
Geometric Coefficient of Variation 72.6
|
—
|
—
|
|
Ratio of AUClast Values of the Metabolite Compared to Parent (MRAUClast) for 1-OH Midazolam/Midazolam on Day -7, Day 1 and Day 14
Day 14
|
30.1 Ratio
Geometric Coefficient of Variation 65.7
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
MRAUCinf is the ratio of AUCinf values of the metabolite compared to parent, corrected for molecular weight, which was calculated by \[AUCinf (metabolite) × MW (parent)\] / \[AUCinf (parent) × MW (metabolite)\]. 1-OH midazolam was the metabolite of midazolam. AUCinf is AUC from time zero to extrapolated infinite time. It is obtained by AUClast + (Clast/kel), where AUClast is the AUC from time zero to the time of last quantifiable concentration (Clast), and kel is the apparent terminal elimination rate constant.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Ratio of AUC From Time Zero Extrapolated to Infinity (AUCinf) Values of the Metabolite Compared to Parent (MRAUCinf) for 1-OH Midazolam/Midazolam on Day -7, Day 1 and Day 14
Day -7
|
4.31 Ratio
Geometric Coefficient of Variation 68.6
|
—
|
—
|
|
Ratio of AUC From Time Zero Extrapolated to Infinity (AUCinf) Values of the Metabolite Compared to Parent (MRAUCinf) for 1-OH Midazolam/Midazolam on Day -7, Day 1 and Day 14
Day 1
|
5.21 Ratio
Geometric Coefficient of Variation 87.8
|
—
|
—
|
|
Ratio of AUC From Time Zero Extrapolated to Infinity (AUCinf) Values of the Metabolite Compared to Parent (MRAUCinf) for 1-OH Midazolam/Midazolam on Day -7, Day 1 and Day 14
Day 14
|
29.5 Ratio
Geometric Coefficient of Variation 70.3
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
MRAUClast is the ratio of AUClast values of the metabolite compared to parent, corrected for molecular weight, which was calculated by \[AUClast (metabolite) × MW (parent)\] / \[AUClast (parent) × MW (metabolite)\]. Paraxanthine was the metabolite of caffeine.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
MRAUClast for Paraxanthine/Caffeine on Day -7, Day 1 and Day 14
Day -7
|
0.392 Ratio
Geometric Coefficient of Variation 37.2
|
—
|
—
|
|
MRAUClast for Paraxanthine/Caffeine on Day -7, Day 1 and Day 14
Day 1
|
0.324 Ratio
Geometric Coefficient of Variation 44.5
|
—
|
—
|
|
MRAUClast for Paraxanthine/Caffeine on Day -7, Day 1 and Day 14
Day 14
|
0.211 Ratio
Geometric Coefficient of Variation 72.3
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
MRAUClast is the ratio of AUClast values of the metabolite compared to parent, corrected for molecular weight, which was calculated by \[AUClast (metabolite) × MW (parent)\] / \[AUClast (parent) × MW (metabolite)\]. 5-OH Omeprazole was the metabolite of omeprazole.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
MRAUClast for 5-OH Omeprazole/Omeprazole on Day -7, Day 1 and Day 14
Day -7
|
0.309 Ratio
Geometric Coefficient of Variation 107.2
|
—
|
—
|
|
MRAUClast for 5-OH Omeprazole/Omeprazole on Day -7, Day 1 and Day 14
Day 1
|
0.282 Ratio
Geometric Coefficient of Variation 87.0
|
—
|
—
|
|
MRAUClast for 5-OH Omeprazole/Omeprazole on Day -7, Day 1 and Day 14
Day 14
|
0.277 Ratio
Geometric Coefficient of Variation 44.6
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
MRAUCinf is the ratio of AUCinf values of the metabolite compared to parent, corrected for molecular weight, which was calculated by \[AUCinf (metabolite) × MW (parent)\] / \[AUCinf (parent) × MW (metabolite)\]. 5-OH Omeprazole was the metabolite of omeprazole. AUCinf is AUC from time zero to extrapolated infinite time. It is obtained by AUClast + (Clast/kel), where AUClast is the AUC from time zero to the time of last quantifiable concentration (Clast), and kel is the apparent terminal elimination rate constant.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=18 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
MRAUCinf for 5-OH Omeprazole/Omeprazole on Day -7, Day 1 and Day 14
Day -7
|
0.312 Ratio
Geometric Coefficient of Variation 119.8
|
—
|
—
|
|
MRAUCinf for 5-OH Omeprazole/Omeprazole on Day -7, Day 1 and Day 14
Day 1
|
0.960 Ratio
Geometric Coefficient of Variation 92.6
|
—
|
—
|
|
MRAUCinf for 5-OH Omeprazole/Omeprazole on Day -7, Day 1 and Day 14
Day 14
|
0.312 Ratio
Geometric Coefficient of Variation 49.8
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 2 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 2 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
MRAUClast is the ratio of AUClast values of the metabolite compared to parent, corrected for molecular weight, which was calculated by \[AUClast (metabolite) × MW (parent)\] / \[AUClast (parent) × MW (metabolite)\]. Hydroxybupropion was the metabolite of bupropion.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=10 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
MRAUClast for Hydroxybupropion/Bupropion on Day -7, Day 1 and Day 14
Day -7
|
3.01 Ratio
Geometric Coefficient of Variation 60.2
|
—
|
—
|
|
MRAUClast for Hydroxybupropion/Bupropion on Day -7, Day 1 and Day 14
Day 1
|
3.88 Ratio
Geometric Coefficient of Variation 47.5
|
—
|
—
|
|
MRAUClast for Hydroxybupropion/Bupropion on Day -7, Day 1 and Day 14
Day 14
|
6.04 Ratio
Geometric Coefficient of Variation 57.5
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21Population: All participants in Arm 3 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days 14 and 21. Number of participants analyzed represents the total number of participants in Arm 3 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
MRAUClast is the ratio of AUClast values of the metabolite compared to parent, corrected for molecular weight, which was calculated by \[AUClast (metabolite) × MW (parent)\] / \[AUClast (parent) × MW (metabolite)\]. LHY746 was the metabolite of encorafenib.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=11 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
MRAUClast for LHY746/Encorafenib in Arm 3 on Day 14 and Day 21
Day 14
|
3.31 Ratio
Geometric Coefficient of Variation 58.9
|
—
|
—
|
|
MRAUClast for LHY746/Encorafenib in Arm 3 on Day 14 and Day 21
Day 21
|
4.62 Ratio
Geometric Coefficient of Variation 43.3
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
MRCmax is the ratio of Cmax values of the metabolite compared to parent, corrected for molecular weight, which was calculated by \[Cmax (metabolite) × MW (parent)\] / \[Cmax (parent) × MW (metabolite)\]. 1-OH midazolam was the metabolite of midazolam.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Ratio of Cmax Values of the Metabolite Compared to Parent (MRCmax) for 1-OH Midazolam/Midazolam on Day -7, Day 1 and Day 14
Day -7
|
4.56 Ratio
Geometric Coefficient of Variation 54.7
|
—
|
—
|
|
Ratio of Cmax Values of the Metabolite Compared to Parent (MRCmax) for 1-OH Midazolam/Midazolam on Day -7, Day 1 and Day 14
Day 1
|
4.36 Ratio
Geometric Coefficient of Variation 62.8
|
—
|
—
|
|
Ratio of Cmax Values of the Metabolite Compared to Parent (MRCmax) for 1-OH Midazolam/Midazolam on Day -7, Day 1 and Day 14
Day 14
|
22.2 Ratio
Geometric Coefficient of Variation 60.6
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
MRCmax is the ratio of Cmax values of the metabolite compared to parent, corrected for molecular weight, which was calculated by \[Cmax (metabolite) × MW (parent)\] / \[Cmax (parent) × MW (metabolite)\]. Paraxanthine was the metabolite of caffeine.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
MRCmax for Paraxanthine/Caffeine on Day -7, Day 1 and Day 14
Day -7
|
0.335 Ratio
Geometric Coefficient of Variation 25.4
|
—
|
—
|
|
MRCmax for Paraxanthine/Caffeine on Day -7, Day 1 and Day 14
Day 1
|
0.285 Ratio
Geometric Coefficient of Variation 36.8
|
—
|
—
|
|
MRCmax for Paraxanthine/Caffeine on Day -7, Day 1 and Day 14
Day 14
|
0.205 Ratio
Geometric Coefficient of Variation 54.9
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
MRCmax is the ratio of Cmax values of the metabolite compared to parent, corrected for molecular weight, which was calculated by \[Cmax (metabolite) × MW (parent)\] / \[Cmax (parent) × MW (metabolite)\]. 5-OH Omeprazole was the metabolite of omeprazole.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
MRCmax for 5-OH Omeprazole/Omeprazole on Day -7, Day 1 and Day 14
Day -7
|
0.273 Ratio
Geometric Coefficient of Variation 115.2
|
—
|
—
|
|
MRCmax for 5-OH Omeprazole/Omeprazole on Day -7, Day 1 and Day 14
Day 1
|
0.244 Ratio
Geometric Coefficient of Variation 83.0
|
—
|
—
|
|
MRCmax for 5-OH Omeprazole/Omeprazole on Day -7, Day 1 and Day 14
Day 14
|
0.227 Ratio
Geometric Coefficient of Variation 48.2
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 2 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 2 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
MRCmax is the ratio of Cmax values of the metabolite compared to parent, corrected for molecular weight, which was calculated by \[Cmax (metabolite) × MW (parent)\] / \[Cmax (parent) × MW (metabolite)\]. Hydroxybupropion was the metabolite of bupropion.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=10 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
MRCmax for Hydroxybupropion/Bupropion on Day -7, Day 1 and Day 14
Day -7
|
1.80 Ratio
Geometric Coefficient of Variation 61.1
|
—
|
—
|
|
MRCmax for Hydroxybupropion/Bupropion on Day -7, Day 1 and Day 14
Day 1
|
2.51 Ratio
Geometric Coefficient of Variation 50.0
|
—
|
—
|
|
MRCmax for Hydroxybupropion/Bupropion on Day -7, Day 1 and Day 14
Day 14
|
3.38 Ratio
Geometric Coefficient of Variation 48.8
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21Population: All participants in Arm 3 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days 14 and 21. Number of participants analyzed represents the total number of participants in Arm 3 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
MRCmax is the ratio of Cmax values of the metabolite compared to parent, corrected for molecular weight, which was calculated by \[Cmax (metabolite) × MW (parent)\] / \[Cmax (parent) × MW (metabolite)\]. LHY746 was the metabolite of encorafenib.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=11 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
MRCmax for LHY746/Encorafenib in Arm 3 on Day 14 and Day 21
Day 14
|
0.883 Ratio
Geometric Coefficient of Variation 72.5
|
—
|
—
|
|
MRCmax for LHY746/Encorafenib in Arm 3 on Day 14 and Day 21
Day 21
|
1.13 Ratio
Geometric Coefficient of Variation 77.6
|
—
|
—
|
SECONDARY outcome
Timeframe: 0 to 8 hours after dosing on Days -7, 1 and 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
Ae0-8 is the amount excreted into the urine over the collection interval of 0 to 8 hours. MRAe0-8 is the ratio of Ae0-8 values of the metabolite compared to parent, corrected for molecular weight. E-3174 was the metabolite of losartan.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Ratio of Ae0-8 Values of the Metabolite Compared to Parent (MRAe0-8) for E-3174/Losartan on Day -7, Day 1 and Day 14
Day -7
|
0.920 Ratio
Geometric Coefficient of Variation 65.6
|
—
|
—
|
|
Ratio of Ae0-8 Values of the Metabolite Compared to Parent (MRAe0-8) for E-3174/Losartan on Day -7, Day 1 and Day 14
Day 1
|
0.921 Ratio
Geometric Coefficient of Variation 100.0
|
—
|
—
|
|
Ratio of Ae0-8 Values of the Metabolite Compared to Parent (MRAe0-8) for E-3174/Losartan on Day -7, Day 1 and Day 14
Day 14
|
0.693 Ratio
Geometric Coefficient of Variation 99.0
|
—
|
—
|
SECONDARY outcome
Timeframe: 0 to 8 hours after dosing on Days -7, 1 and 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
Ae0-8 is the amount excreted into the urine over the collection interval of 0 to 8 hours. MRAe0-8 is the ratio of Ae0-8 values of the metabolite compared to parent, corrected for molecular weight. Dextrorphan was the metabolite of dextromethorphan.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
MRAe0-8 for Dextrorphan/Dextromethorphan on Day -7, Day 1 and Day 14
Day -7
|
151 Ratio
Geometric Coefficient of Variation 383.2
|
—
|
—
|
|
MRAe0-8 for Dextrorphan/Dextromethorphan on Day -7, Day 1 and Day 14
Day 1
|
144 Ratio
Geometric Coefficient of Variation 560.9
|
—
|
—
|
|
MRAe0-8 for Dextrorphan/Dextromethorphan on Day -7, Day 1 and Day 14
Day 14
|
167 Ratio
Geometric Coefficient of Variation 354.5
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
Tmax is time to reach maximum observed plasma concentration. It was observed directly from the concentration-time data.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Time to Reach Cmax (Tmax) of Plasma Midazolam on Day -7, Day 1 and Day 14
Day 14
|
0.88 Hours
Interval 0.68 to 1.0
|
—
|
—
|
|
Time to Reach Cmax (Tmax) of Plasma Midazolam on Day -7, Day 1 and Day 14
Day -7
|
1.00 Hours
Interval 0.77 to 2.93
|
—
|
—
|
|
Time to Reach Cmax (Tmax) of Plasma Midazolam on Day -7, Day 1 and Day 14
Day 1
|
0.88 Hours
Interval 0.77 to 1.3
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14.Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
Tmax is time to reach maximum observed plasma concentration. It was observed directly from the concentration-time data. The metabolites of midazolam included total 1-OH midazolam, free 1-OH midazolam, and glucuronide conjugated 1-hydroxymidazolam.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Tmax of Plasma Total 1-OH Midazolam on Day -7, Day 1 and Day 14
Day -7
|
1.00 Hours
Interval 0.77 to 2.93
|
—
|
—
|
|
Tmax of Plasma Total 1-OH Midazolam on Day -7, Day 1 and Day 14
Day 1
|
0.90 Hours
Interval 0.8 to 1.85
|
—
|
—
|
|
Tmax of Plasma Total 1-OH Midazolam on Day -7, Day 1 and Day 14
Day 14
|
0.88 Hours
Interval 0.68 to 1.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
Tmax is time to reach maximum observed plasma concentration. It was observed directly from the concentration-time data. The metabolites of midazolam included total 1-OH midazolam, free 1-OH midazolam, and glucuronide conjugated 1-hydroxymidazolam.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Tmax of Plasma Free 1-OH Midazolam on Day -7, Day 1 and Day 14
Day -7
|
1.00 Hours
Interval 0.77 to 2.93
|
—
|
—
|
|
Tmax of Plasma Free 1-OH Midazolam on Day -7, Day 1 and Day 14
Day 1
|
0.90 Hours
Interval 0.8 to 1.85
|
—
|
—
|
|
Tmax of Plasma Free 1-OH Midazolam on Day -7, Day 1 and Day 14
Day 14
|
0.92 Hours
Interval 0.68 to 1.72
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
Tmax is time to reach maximum observed plasma concentration. It was observed directly from the concentration-time data. The metabolites of midazolam included total 1-OH midazolam, free 1-OH midazolam, and glucuronide conjugated 1-hydroxymidazolam.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Tmax of Plasma Glucuronide Conjugated 1-Hydroxymidazolam on Day -7, Day 1 and Day 14
Day -7
|
1.00 Hours
Interval 0.77 to 2.97
|
—
|
—
|
|
Tmax of Plasma Glucuronide Conjugated 1-Hydroxymidazolam on Day -7, Day 1 and Day 14
Day 1
|
0.90 Hours
Interval 0.8 to 1.83
|
—
|
—
|
|
Tmax of Plasma Glucuronide Conjugated 1-Hydroxymidazolam on Day -7, Day 1 and Day 14
Day 14
|
0.88 Hours
Interval 0.68 to 1.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
Tmax is time to reach maximum observed plasma concentration. It was observed directly from the concentration-time data. Due to dietary caffeine intake may resulted in positive pre-dose concentrations, absolute and/or baseline-adjusted caffeine were analyzed. Baseline adjusted concentration = measured concentration - \[predose concentration\*e\^(-Kel\*t)\], where Kel is terminal elimination rate constant based on actual measured concentration values for each profile and t is the actual sampling time.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Tmax of Plasma Absolute Caffeine on Day -7, Day 1 and Day 14
Day -7
|
1.00 Hours
Interval 0.8 to 1.98
|
—
|
—
|
|
Tmax of Plasma Absolute Caffeine on Day -7, Day 1 and Day 14
Day 1
|
0.93 Hours
Interval 0.78 to 1.88
|
—
|
—
|
|
Tmax of Plasma Absolute Caffeine on Day -7, Day 1 and Day 14
Day 14
|
0.90 Hours
Interval 0.72 to 2.92
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
Tmax is time to reach maximum observed plasma concentration. It was observed directly from the concentration-time data. Due to dietary caffeine intake may resulted in positive pre-dose concentrations, absolute and/or baseline-adjusted caffeine were analyzed. Baseline adjusted concentration = measured concentration - \[predose concentration\*e\^(-Kel\*t)\], where Kel is terminal elimination rate constant based on actual measured concentration values for each profile and t is the actual sampling time.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Tmax of Plasma Baseline-Adjusted Caffeine on Day -7, Day 1 and Day 14
Day -7
|
1.00 Hours
Interval 0.8 to 2.17
|
—
|
—
|
|
Tmax of Plasma Baseline-Adjusted Caffeine on Day -7, Day 1 and Day 14
Day 1
|
0.94 Hours
Interval 0.78 to 1.88
|
—
|
—
|
|
Tmax of Plasma Baseline-Adjusted Caffeine on Day -7, Day 1 and Day 14
Day 14
|
0.98 Hours
Interval 0.72 to 3.97
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
Tmax is time to reach maximum observed plasma concentration. It was observed directly from the concentration-time data. Paraxanthine was the metabolite of caffeine.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Tmax of Plasma Paraxanthine on Day -7, Day 1 and Day 14
Day -7
|
7.18 Hours
Interval 3.77 to 7.98
|
—
|
—
|
|
Tmax of Plasma Paraxanthine on Day -7, Day 1 and Day 14
Day 1
|
7.63 Hours
Interval 1.83 to 7.92
|
—
|
—
|
|
Tmax of Plasma Paraxanthine on Day -7, Day 1 and Day 14
Day 14
|
6.00 Hours
Interval 2.13 to 8.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours (+/- 15 minutes window for each time-point) postdose on Day 1 and Day 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
Tmax is time to reach maximum observed plasma concentration. It was observed directly from the concentration-time data.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Tmax of Plasma Omeprazole on Day -7, Day 1 and Day 14
Day -7
|
2.20 Hours
Interval 1.05 to 8.07
|
—
|
—
|
|
Tmax of Plasma Omeprazole on Day -7, Day 1 and Day 14
Day 1
|
3.00 Hours
Interval 0.87 to 7.92
|
—
|
—
|
|
Tmax of Plasma Omeprazole on Day -7, Day 1 and Day 14
Day 14
|
3.00 Hours
Interval 0.85 to 7.85
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours (+/- 15 minutes window for each time-point) postdose on Day 1 and Day 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
Tmax is time to reach maximum observed plasma concentration. It was observed directly from the concentration-time data. 5-OH Omeprazole was the metabolite of omeprazole.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Tmax of Plasma 5-OH Omeprazole on Day -7, Day 1 and Day 14
Day -7
|
2.97 Hours
Interval 0.0 to 8.07
|
—
|
—
|
|
Tmax of Plasma 5-OH Omeprazole on Day -7, Day 1 and Day 14
Day 1
|
3.80 Hours
Interval 0.87 to 7.92
|
—
|
—
|
|
Tmax of Plasma 5-OH Omeprazole on Day -7, Day 1 and Day 14
Day 14
|
3.00 Hours
Interval 0.85 to 7.85
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 2 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 2 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
Tmax is time to reach maximum observed plasma concentration. It was observed directly from the concentration-time data.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=10 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Tmax of Plasma Rosuvastatin on Day -7, Day 1 and Day 14
Day -7
|
2.40 Hours
Interval 1.0 to 4.02
|
—
|
—
|
|
Tmax of Plasma Rosuvastatin on Day -7, Day 1 and Day 14
Day 1
|
1.85 Hours
Interval 0.78 to 7.0
|
—
|
—
|
|
Tmax of Plasma Rosuvastatin on Day -7, Day 1 and Day 14
Day 14
|
1.40 Hours
Interval 0.92 to 3.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 2 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 2 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
Tmax is time to reach maximum observed plasma concentration. It was observed directly from the concentration-time data.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=10 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Tmax of Plasma Bupropion on Day -7, Day 1 and Day 14
Day -7
|
1.87 Hours
Interval 0.82 to 4.0
|
—
|
—
|
|
Tmax of Plasma Bupropion on Day -7, Day 1 and Day 14
Day 1
|
1.93 Hours
Interval 0.77 to 4.0
|
—
|
—
|
|
Tmax of Plasma Bupropion on Day -7, Day 1 and Day 14
Day 14
|
1.92 Hours
Interval 0.93 to 2.87
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 2 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 2 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
Tmax is time to reach maximum observed plasma concentration. It was observed directly from the concentration-time data. Hydroxybupropion was the metabolite of bupropion.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=10 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Tmax of Plasma Hydroxybupropion on Day -7, Day 1 and Day 14
Day -7
|
4.00 Hours
Interval 3.0 to 8.0
|
—
|
—
|
|
Tmax of Plasma Hydroxybupropion on Day -7, Day 1 and Day 14
Day 1
|
7.68 Hours
Interval 3.83 to 8.0
|
—
|
—
|
|
Tmax of Plasma Hydroxybupropion on Day -7, Day 1 and Day 14
Day 14
|
3.94 Hours
Interval 1.0 to 6.17
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
AUCinf is AUC from time zero to extrapolated infinite time. It is obtained by AUClast + (Clast/kel), where AUClast is the AUC from time zero to the time of last quantifiable concentration (Clast), and kel is the apparent terminal elimination rate constant.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
AUCinf of Plasma Midazolam on Day -7, Day 1 and Day 14
Day -7
|
27.1 ng*hr/mL
Geometric Coefficient of Variation 72.5
|
—
|
—
|
|
AUCinf of Plasma Midazolam on Day -7, Day 1 and Day 14
Day 1
|
27.1 ng*hr/mL
Geometric Coefficient of Variation 65.1
|
—
|
—
|
|
AUCinf of Plasma Midazolam on Day -7, Day 1 and Day 14
Day 14
|
5.10 ng*hr/mL
Geometric Coefficient of Variation 52.5
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
AUCinf is AUC from time zero to extrapolated infinite time. It is obtained by AUClast + (Clast/kel), where AUClast is the AUC from time zero to the time of last quantifiable concentration (Clast), and kel is the apparent terminal elimination rate constant. The metabolites of midazolam included total 1-OH midazolam, free 1-OH midazolam, and glucuronide conjugated 1-hydroxymidazolam.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
AUCinf of Plasma Total 1-OH Midazolam on Day -7, Day 1 and Day 14
Day -7
|
150 ng*hr/mL
Geometric Coefficient of Variation 27.7
|
—
|
—
|
|
AUCinf of Plasma Total 1-OH Midazolam on Day -7, Day 1 and Day 14
Day 1
|
172 ng*hr/mL
Geometric Coefficient of Variation 49.1
|
—
|
—
|
|
AUCinf of Plasma Total 1-OH Midazolam on Day -7, Day 1 and Day 14
Day 14
|
154 ng*hr/mL
Geometric Coefficient of Variation 35.5
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
AUCinf is AUC from time zero to extrapolated infinite time. It is obtained by AUClast + (Clast/kel), where AUClast is the AUC from time zero to the time of last quantifiable concentration (Clast), and kel is the apparent terminal elimination rate constant. The metabolites of midazolam included total 1-OH midazolam, free 1-OH midazolam, and glucuronide conjugated 1-hydroxymidazolam.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
AUCinf of Plasma Free 1-OH Midazolam on Day -7, Day 1 and Day 14
Day -7
|
9.98 ng*hr/mL
Geometric Coefficient of Variation 43.9
|
—
|
—
|
|
AUCinf of Plasma Free 1-OH Midazolam on Day -7, Day 1 and Day 14
Day 1
|
13.1 ng*hr/mL
Geometric Coefficient of Variation 44.9
|
—
|
—
|
|
AUCinf of Plasma Free 1-OH Midazolam on Day -7, Day 1 and Day 14
Day 14
|
5.52 ng*hr/mL
Geometric Coefficient of Variation 56.2
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
AUCinf is AUC from time zero to extrapolated infinite time. It is obtained by AUClast + (Clast/kel), where AUClast is the AUC from time zero to the time of last quantifiable concentration (Clast), and kel is the apparent terminal elimination rate constant. The metabolites of midazolam included total 1-OH midazolam, free 1-OH midazolam, and glucuronide conjugated 1-hydroxymidazolam.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
AUCinf of Plasma Glucuronide Conjugated 1-Hydroxymidazolam on Day -7, Day 1 and Day 14
Day -7
|
139 ng*hr/mL
Geometric Coefficient of Variation 30.6
|
—
|
—
|
|
AUCinf of Plasma Glucuronide Conjugated 1-Hydroxymidazolam on Day -7, Day 1 and Day 14
Day 1
|
167 ng*hr/mL
Geometric Coefficient of Variation 52.4
|
—
|
—
|
|
AUCinf of Plasma Glucuronide Conjugated 1-Hydroxymidazolam on Day -7, Day 1 and Day 14
Day 14
|
143 ng*hr/mL
Geometric Coefficient of Variation 36.3
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
AUCinf is AUC from time zero to extrapolated infinite time. It is obtained by AUClast + (Clast/kel), where AUClast is the AUC from time zero to the time of last quantifiable concentration (Clast), and kel is the apparent terminal elimination rate constant.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
AUCinf of Plasma Omeprazole on Day -7, Day 1 and Day 14
Day -7
|
1630 ng*hr/mL
Geometric Coefficient of Variation 151.6
|
—
|
—
|
|
AUCinf of Plasma Omeprazole on Day -7, Day 1 and Day 14
Day 1
|
1170 ng*hr/mL
Geometric Coefficient of Variation 79.4
|
—
|
—
|
|
AUCinf of Plasma Omeprazole on Day -7, Day 1 and Day 14
Day 14
|
904 ng*hr/mL
Geometric Coefficient of Variation 35.7
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
AUCinf is AUC from time zero to extrapolated infinite time. It is obtained by AUClast + (Clast/kel), where AUClast is the AUC from time zero to the time of last quantifiable concentration (Clast), and kel is the apparent terminal elimination rate constant. 5-OH Omeprazole was the metabolite of omeprazole.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=18 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
AUCinf of Plasma 5-OH Omeprazole on Day -7, Day 1 and Day 14
Day -7
|
557 ng*hr/mL
Geometric Coefficient of Variation 92.6
|
—
|
—
|
|
AUCinf of Plasma 5-OH Omeprazole on Day -7, Day 1 and Day 14
Day 1
|
880 ng*hr/mL
Geometric Coefficient of Variation 21.8
|
—
|
—
|
|
AUCinf of Plasma 5-OH Omeprazole on Day -7, Day 1 and Day 14
Day 14
|
294 ng*hr/mL
Geometric Coefficient of Variation 44.5
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 2 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 2 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
AUCinf is AUC from time zero to extrapolated infinite time. It is obtained by AUClast + (Clast/kel), where AUClast is the AUC from time zero to the time of last quantifiable concentration (Clast), and kel is the apparent terminal elimination rate constant.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=10 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
AUCinf of Plasma Rosuvastatin on Day -7, Day 1 and Day 14
Day -7
|
75.4 ng*hr/mL
Geometric Coefficient of Variation 62.3
|
—
|
—
|
|
AUCinf of Plasma Rosuvastatin on Day -7, Day 1 and Day 14
Day 1
|
139 ng*hr/mL
Geometric Coefficient of Variation 69.8
|
—
|
—
|
|
AUCinf of Plasma Rosuvastatin on Day -7, Day 1 and Day 14
Day 14
|
62.9 ng*hr/mL
Geometric Coefficient of Variation 48.5
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 2 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 2 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
AUCinf is AUC from time zero to extrapolated infinite time. It is obtained by AUClast + (Clast/kel), where AUClast is the AUC from time zero to the time of last quantifiable concentration (Clast), and kel is the apparent terminal elimination rate constant.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=10 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
AUCinf of Plasma Bupropion on Day -7, Day 1 and Day 14
Day -7
|
398 ng*hr/mL
Geometric Coefficient of Variation 54.9
|
—
|
—
|
|
AUCinf of Plasma Bupropion on Day -7, Day 1 and Day 14
Day 1
|
390 ng*hr/mL
Geometric Coefficient of Variation 11.1
|
—
|
—
|
|
AUCinf of Plasma Bupropion on Day -7, Day 1 and Day 14
Day 14
|
298 ng*hr/mL
Geometric Coefficient of Variation 38.4
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
AUC%extrap is the percentage of AUCinf obtained by forward extrapolation. It is calculated as (AUCinf minus AUClast)\*100/ AUCinf.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Percent of AUC Extrapolated (AUC%Extrap) of Plasma Midazolam on Day -7, Day 1 and Day 14
Day -7
|
19.1 percentage of AUC
Geometric Coefficient of Variation 46.0
|
—
|
—
|
|
Percent of AUC Extrapolated (AUC%Extrap) of Plasma Midazolam on Day -7, Day 1 and Day 14
Day 1
|
19.3 percentage of AUC
Geometric Coefficient of Variation 37.6
|
—
|
—
|
|
Percent of AUC Extrapolated (AUC%Extrap) of Plasma Midazolam on Day -7, Day 1 and Day 14
Day 14
|
8.76 percentage of AUC
Geometric Coefficient of Variation 55.2
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
AUC%extrap is the percentage of AUCinf obtained by forward extrapolation. It is calculated as (AUCinf minus AUClast)\*100/ AUCinf. The metabolites of midazolam included total 1-OH midazolam, free 1-OH midazolam, and glucuronide conjugated 1-hydroxymidazolam.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
AUC%Extrap of Plasma Total 1-OH Midazolam on Day -7, Day 1 and Day 14
Day -7
|
15.2 Percentage of AUC
Geometric Coefficient of Variation 35.2
|
—
|
—
|
|
AUC%Extrap of Plasma Total 1-OH Midazolam on Day -7, Day 1 and Day 14
Day 1
|
21.9 Percentage of AUC
Geometric Coefficient of Variation 40.1
|
—
|
—
|
|
AUC%Extrap of Plasma Total 1-OH Midazolam on Day -7, Day 1 and Day 14
Day 14
|
12.6 Percentage of AUC
Geometric Coefficient of Variation 68.4
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
AUC%extrap is the percentage of AUCinf obtained by forward extrapolation. It is calculated as (AUCinf minus AUClast)\*100/ AUCinf. The metabolites of midazolam included total 1-OH midazolam, free 1-OH midazolam, and glucuronide conjugated 1-hydroxymidazolam.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
AUC%Extrap of Plasma Free 1-OH Midazolam on Day -7, Day 1 and Day 14
Day -7
|
14.1 Percentage of AUC
Geometric Coefficient of Variation 42.6
|
—
|
—
|
|
AUC%Extrap of Plasma Free 1-OH Midazolam on Day -7, Day 1 and Day 14
Day 1
|
12.9 Percentage of AUC
Geometric Coefficient of Variation 46.1
|
—
|
—
|
|
AUC%Extrap of Plasma Free 1-OH Midazolam on Day -7, Day 1 and Day 14
Day 14
|
12.8 Percentage of AUC
Geometric Coefficient of Variation 68.1
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
AUC%extrap is the percentage of AUCinf obtained by forward extrapolation. It is calculated as (AUCinf minus AUClast)\*100/ AUCinf. The metabolites of midazolam included total 1-OH midazolam, free 1-OH midazolam, and glucuronide conjugated 1-hydroxymidazolam.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
AUC%Extrap of Plasma Glucuronide Conjugated 1-Hydroxymidazolam on Day -7, Day 1 and Day 14
Day -7
|
15.3 Percentage of AUC
Geometric Coefficient of Variation 35.0
|
—
|
—
|
|
AUC%Extrap of Plasma Glucuronide Conjugated 1-Hydroxymidazolam on Day -7, Day 1 and Day 14
Day 1
|
22.6 Percentage of AUC
Geometric Coefficient of Variation 40.5
|
—
|
—
|
|
AUC%Extrap of Plasma Glucuronide Conjugated 1-Hydroxymidazolam on Day -7, Day 1 and Day 14
Day 14
|
14.1 Percentage of AUC
Geometric Coefficient of Variation 54.9
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
AUC%extrap is the percentage of AUCinf obtained by forward extrapolation. It is calculated as (AUCinf minus AUClast)\*100/ AUCinf. Due to dietary caffeine intake may resulted in positive pre-dose concentrations, absolute and/or baseline-adjusted caffeine were analyzed. Baseline adjusted concentration = measured concentration - \[predose concentration\*e\^(-Kel\*t)\], where Kel is terminal elimination rate constant based on actual measured concentration values for each profile and t is the actual sampling time.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
AUC%Extrap of Plasma Absolute Caffeine on Day -7, Day 1 and Day 14
Day -7
|
48.3 Percentage of AUC
Geometric Coefficient of Variation 39.4
|
—
|
—
|
|
AUC%Extrap of Plasma Absolute Caffeine on Day -7, Day 1 and Day 14
Day 1
|
53.2 Percentage of AUC
Geometric Coefficient of Variation 27.0
|
—
|
—
|
|
AUC%Extrap of Plasma Absolute Caffeine on Day -7, Day 1 and Day 14
Day 14
|
61.0 Percentage of AUC
Geometric Coefficient of Variation 26.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
AUC%extrap is the percentage of AUCinf obtained by forward extrapolation. It is calculated as (AUCinf minus AUClast)\*100/ AUCinf. Due to dietary caffeine intake may resulted in positive pre-dose concentrations, absolute and/or baseline-adjusted caffeine were analyzed. Baseline adjusted concentration = measured concentration - \[predose concentration\*e\^(-Kel\*t)\], where Kel is terminal elimination rate constant based on actual measured concentration values for each profile and t is the actual sampling time.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
AUC%Extrap of Plasma Baseline-Adjusted Caffeine on Day -7, Day 1 and Day 14
Day -7
|
46.7 Percentage of AUC
Geometric Coefficient of Variation 37.6
|
—
|
—
|
|
AUC%Extrap of Plasma Baseline-Adjusted Caffeine on Day -7, Day 1 and Day 14
Day 1
|
54.8 Percentage of AUC
Geometric Coefficient of Variation 25.5
|
—
|
—
|
|
AUC%Extrap of Plasma Baseline-Adjusted Caffeine on Day -7, Day 1 and Day 14
Day 14
|
58.0 Percentage of AUC
Geometric Coefficient of Variation 25.3
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
AUC%extrap is the percentage of AUCinf obtained by forward extrapolation. It is calculated as (AUCinf minus AUClast)\*100/ AUCinf.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
AUC%Extrap of Plasma Omeprazole on Day -7, Day 1 and Day 14
Day -7
|
7.35 Percentage of AUC
Geometric Coefficient of Variation 142.1
|
—
|
—
|
|
AUC%Extrap of Plasma Omeprazole on Day -7, Day 1 and Day 14
Day 1
|
11.9 Percentage of AUC
Geometric Coefficient of Variation 141.2
|
—
|
—
|
|
AUC%Extrap of Plasma Omeprazole on Day -7, Day 1 and Day 14
Day 14
|
4.22 Percentage of AUC
Geometric Coefficient of Variation 113.9
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
AUC%extrap is the percentage of AUCinf obtained by forward extrapolation. It is calculated as (AUCinf minus AUClast)\*100/ AUCinf. 5-OH Omeprazole was the metabolite of omeprazole.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
AUC%Extrap of Plasma 5-OH Omeprazole on Day -7, Day 1 and Day 14
Day -7
|
12.4 Percentage of AUC
Geometric Coefficient of Variation 147.3
|
—
|
—
|
|
AUC%Extrap of Plasma 5-OH Omeprazole on Day -7, Day 1 and Day 14
Day 1
|
26.1 Percentage of AUC
Geometric Coefficient of Variation 65.7
|
—
|
—
|
|
AUC%Extrap of Plasma 5-OH Omeprazole on Day -7, Day 1 and Day 14
Day 14
|
8.07 Percentage of AUC
Geometric Coefficient of Variation 66.7
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
Kel is the apparent terminal elimination rate constant, which is estimated by linear regression of time versus loge concentration.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Apparent Terminal Elimination Rate Constant (Kel) of Plasma Midazolam on Day -7, Day 1 and Day 14
Day 14
|
0.347 Fraction/hour
Geometric Coefficient of Variation 55.4
|
—
|
—
|
|
Apparent Terminal Elimination Rate Constant (Kel) of Plasma Midazolam on Day -7, Day 1 and Day 14
Day -7
|
0.196 Fraction/hour
Geometric Coefficient of Variation 26.2
|
—
|
—
|
|
Apparent Terminal Elimination Rate Constant (Kel) of Plasma Midazolam on Day -7, Day 1 and Day 14
Day 1
|
0.188 Fraction/hour
Geometric Coefficient of Variation 22.6
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
Kel is the apparent terminal elimination rate constant, which is estimated by linear regression of time versus loge concentration. The metabolites of midazolam included total 1-OH midazolam, free 1-OH midazolam, and glucuronide conjugated 1-hydroxymidazolam.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Kel of Plasma Total 1-OH Midazolam on Day -7, Day 1 and Day 14
Day -7
|
0.248 Fraction/hour
Geometric Coefficient of Variation 20.1
|
—
|
—
|
|
Kel of Plasma Total 1-OH Midazolam on Day -7, Day 1 and Day 14
Day 1
|
0.199 Fraction/hour
Geometric Coefficient of Variation 31.3
|
—
|
—
|
|
Kel of Plasma Total 1-OH Midazolam on Day -7, Day 1 and Day 14
Day 14
|
0.259 Fraction/hour
Geometric Coefficient of Variation 36.9
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
Kel is the apparent terminal elimination rate constant, which is estimated by linear regression of time versus loge concentration. The metabolites of midazolam included total 1-OH midazolam, free 1-OH midazolam, and glucuronide conjugated 1-hydroxymidazolam.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Kel of Plasma Free 1-OH Midazolam on Day -7, Day 1 and Day 14
Day -7
|
0.231 Fraction/hour
Geometric Coefficient of Variation 24.2
|
—
|
—
|
|
Kel of Plasma Free 1-OH Midazolam on Day -7, Day 1 and Day 14
Day 1
|
0.236 Fraction/hour
Geometric Coefficient of Variation 31.1
|
—
|
—
|
|
Kel of Plasma Free 1-OH Midazolam on Day -7, Day 1 and Day 14
Day 14
|
0.269 Fraction/hour
Geometric Coefficient of Variation 47.2
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
Kel is the apparent terminal elimination rate constant, which is estimated by linear regression of time versus loge concentration. The metabolites of midazolam included total 1-OH midazolam, free 1-OH midazolam, and glucuronide conjugated 1-hydroxymidazolam.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Kel of Plasma Glucuronide Conjugated 1-Hydroxymidazolam on Day -7, Day 1 and Day 14
Day -7
|
0.241 Fraction/hour
Geometric Coefficient of Variation 23.3
|
—
|
—
|
|
Kel of Plasma Glucuronide Conjugated 1-Hydroxymidazolam on Day -7, Day 1 and Day 14
Day 1
|
0.197 Fraction/hour
Geometric Coefficient of Variation 32.5
|
—
|
—
|
|
Kel of Plasma Glucuronide Conjugated 1-Hydroxymidazolam on Day -7, Day 1 and Day 14
Day 14
|
0.277 Fraction/hour
Geometric Coefficient of Variation 37.7
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
Kel is the apparent terminal elimination rate constant, which is estimated by linear regression of time versus loge concentration. Due to dietary caffeine intake may resulted in positive pre-dose concentrations, absolute and/or baseline-adjusted caffeine were analyzed. Baseline adjusted concentration = measured concentration - \[predose concentration\*e\^(-Kel\*t)\], where Kel is terminal elimination rate constant based on actual measured concentration values for each profile and t is the actual sampling time.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Kel of Plasma Absolute Caffeine on Day -7, Day 1 and Day 14
Day -7
|
0.0870 Fraction/hour
Geometric Coefficient of Variation 57.4
|
—
|
—
|
|
Kel of Plasma Absolute Caffeine on Day -7, Day 1 and Day 14
Day 1
|
0.0753 Fraction/hour
Geometric Coefficient of Variation 61.3
|
—
|
—
|
|
Kel of Plasma Absolute Caffeine on Day -7, Day 1 and Day 14
Day 14
|
0.0575 Fraction/hour
Geometric Coefficient of Variation 61.7
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
Kel is the apparent terminal elimination rate constant, which is estimated by linear regression of time versus loge concentration. Due to dietary caffeine intake may resulted in positive pre-dose concentrations, absolute and/or baseline-adjusted caffeine were analyzed. Baseline adjusted concentration = measured concentration - \[predose concentration\*e\^(-Kel\*t)\], where Kel is terminal elimination rate constant based on actual measured concentration values for each profile and t is the actual sampling time.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Kel of Plasma Baseline-Adjusted Caffeine on Day -7, Day 1 and Day 14
Day -7
|
0.0893 Fraction/hour
Geometric Coefficient of Variation 70.3
|
—
|
—
|
|
Kel of Plasma Baseline-Adjusted Caffeine on Day -7, Day 1 and Day 14
Day 1
|
0.0739 Fraction/hour
Geometric Coefficient of Variation 58.3
|
—
|
—
|
|
Kel of Plasma Baseline-Adjusted Caffeine on Day -7, Day 1 and Day 14
Day 14
|
0.0656 Fraction/hour
Geometric Coefficient of Variation 54.4
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
Kel is the apparent terminal elimination rate constant, which is estimated by linear regression of time versus loge concentration.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Kel of Plasma Omeprazole on Day -7, Day 1 and Day 14
Day -7
|
0.401 Fraction/hour
Geometric Coefficient of Variation 50.4
|
—
|
—
|
|
Kel of Plasma Omeprazole on Day -7, Day 1 and Day 14
Day 1
|
0.296 Fraction/hour
Geometric Coefficient of Variation 53.1
|
—
|
—
|
|
Kel of Plasma Omeprazole on Day -7, Day 1 and Day 14
Day 14
|
0.461 Fraction/hour
Geometric Coefficient of Variation 31.1
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
Kel is the apparent terminal elimination rate constant, which is estimated by linear regression of time versus loge concentration. 5-OH Omeprazole was the metabolite of omeprazole.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Kel of Plasma 5-OH Omeprazole on Day -7, Day 1 and Day 14
Day -7
|
0.303 Fraction/hour
Geometric Coefficient of Variation 43.1
|
—
|
—
|
|
Kel of Plasma 5-OH Omeprazole on Day -7, Day 1 and Day 14
Day 1
|
0.197 Fraction/hour
Geometric Coefficient of Variation 45.7
|
—
|
—
|
|
Kel of Plasma 5-OH Omeprazole on Day -7, Day 1 and Day 14
Day 14
|
0.386 Fraction/hour
Geometric Coefficient of Variation 22.5
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14.Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
T1/2 is the terminal elimination half-life, which is estimated by Loge(2) / kel, where kel is the apparent terminal elimination rate constant.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Terminal Elimination Half-Life (T1/2) of Plasma Midazolam on Day -7, Day 1 and Day 14
Day -7
|
3.54 Hours
Geometric Coefficient of Variation 26.2
|
—
|
—
|
|
Terminal Elimination Half-Life (T1/2) of Plasma Midazolam on Day -7, Day 1 and Day 14
Day 1
|
3.69 Hours
Geometric Coefficient of Variation 22.6
|
—
|
—
|
|
Terminal Elimination Half-Life (T1/2) of Plasma Midazolam on Day -7, Day 1 and Day 14
Day 14
|
2.00 Hours
Geometric Coefficient of Variation 55.4
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
T1/2 is the terminal elimination half-life, which is estimated by Loge(2) / kel, where kel is the apparent terminal elimination rate constant. The metabolites of midazolam included total 1-OH midazolam, free 1-OH midazolam, and glucuronide conjugated 1-hydroxymidazolam.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
T1/2 of Plasma Total 1-OH Midazolam on Day -7, Day 1 and Day 14
Day -7
|
2.80 Hours
Geometric Coefficient of Variation 20.1
|
—
|
—
|
|
T1/2 of Plasma Total 1-OH Midazolam on Day -7, Day 1 and Day 14
Day 1
|
3.48 Hours
Geometric Coefficient of Variation 31.3
|
—
|
—
|
|
T1/2 of Plasma Total 1-OH Midazolam on Day -7, Day 1 and Day 14
Day 14
|
2.68 Hours
Geometric Coefficient of Variation 36.9
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
T1/2 is the terminal elimination half-life, which is estimated by Loge(2) / kel, where kel is the apparent terminal elimination rate constant. The metabolites of midazolam included total 1-OH midazolam, free 1-OH midazolam, and glucuronide conjugated 1-hydroxymidazolam.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
T1/2 of Plasma Free 1-OH Midazolam on Day -7, Day 1 and Day 14
Day -7
|
3.00 Hours
Geometric Coefficient of Variation 24.2
|
—
|
—
|
|
T1/2 of Plasma Free 1-OH Midazolam on Day -7, Day 1 and Day 14
Day 1
|
2.93 Hours
Geometric Coefficient of Variation 31.1
|
—
|
—
|
|
T1/2 of Plasma Free 1-OH Midazolam on Day -7, Day 1 and Day 14
Day 14
|
2.58 Hours
Geometric Coefficient of Variation 47.2
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14.Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
T1/2 is the terminal elimination half-life, which is estimated by Loge(2) / kel, where kel is the apparent terminal elimination rate constant. The metabolites of midazolam included total 1-OH midazolam, free 1-OH midazolam, and glucuronide conjugated 1-hydroxymidazolam.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
T1/2 of Plasma Glucuronide Conjugated 1-Hydroxymidazolam on Day -7, Day 1 and Day 14
Day -7
|
2.87 Hours
Geometric Coefficient of Variation 23.3
|
—
|
—
|
|
T1/2 of Plasma Glucuronide Conjugated 1-Hydroxymidazolam on Day -7, Day 1 and Day 14
Day 1
|
3.53 Hours
Geometric Coefficient of Variation 32.5
|
—
|
—
|
|
T1/2 of Plasma Glucuronide Conjugated 1-Hydroxymidazolam on Day -7, Day 1 and Day 14
Day 14
|
2.50 Hours
Geometric Coefficient of Variation 37.7
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
T1/2 is the terminal elimination half-life, which is estimated by Loge(2) / kel, where kel is the apparent terminal elimination rate constant. Due to dietary caffeine intake may resulted in positive pre-dose concentrations, absolute and/or baseline-adjusted caffeine were analyzed. Baseline adjusted concentration = measured concentration - \[predose concentration\*e\^(-Kel\*t)\], where Kel is terminal elimination rate constant based on actual measured concentration values for each profile and t is the actual sampling time.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
T1/2 of Plasma Absolute Caffeine on Day -7, Day 1 and Day 14
Day -7
|
7.97 Hours
Geometric Coefficient of Variation 57.4
|
—
|
—
|
|
T1/2 of Plasma Absolute Caffeine on Day -7, Day 1 and Day 14
Day 1
|
9.20 Hours
Geometric Coefficient of Variation 61.3
|
—
|
—
|
|
T1/2 of Plasma Absolute Caffeine on Day -7, Day 1 and Day 14
Day 14
|
12.1 Hours
Geometric Coefficient of Variation 61.7
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
T1/2 is the terminal elimination half-life, which is estimated by Loge(2) / kel, where kel is the apparent terminal elimination rate constant. Due to dietary caffeine intake may resulted in positive pre-dose concentrations, absolute and/or baseline-adjusted caffeine were analyzed. Baseline adjusted concentration = measured concentration - \[predose concentration\*e\^(-Kel\*t)\], where Kel is terminal elimination rate constant based on actual measured concentration values for each profile and t is the actual sampling time.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
T1/2 of Plasma Baseline-Adjusted Caffeine on Day -7, Day 1 and Day 14
Day -7
|
7.76 Hours
Geometric Coefficient of Variation 70.3
|
—
|
—
|
|
T1/2 of Plasma Baseline-Adjusted Caffeine on Day -7, Day 1 and Day 14
Day 1
|
9.38 Hours
Geometric Coefficient of Variation 58.3
|
—
|
—
|
|
T1/2 of Plasma Baseline-Adjusted Caffeine on Day -7, Day 1 and Day 14
Day 14
|
10.6 Hours
Geometric Coefficient of Variation 54.4
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
T1/2 is the terminal elimination half-life, which is estimated by Loge(2) / kel, where kel is the apparent terminal elimination rate constant.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
T1/2 of Plasma Omeprazole on Day -7, Day 1 and Day 14
Day -7
|
1.73 Hours
Geometric Coefficient of Variation 50.4
|
—
|
—
|
|
T1/2 of Plasma Omeprazole on Day -7, Day 1 and Day 14
Day 1
|
2.34 Hours
Geometric Coefficient of Variation 53.1
|
—
|
—
|
|
T1/2 of Plasma Omeprazole on Day -7, Day 1 and Day 14
Day 14
|
1.50 Hours
Geometric Coefficient of Variation 31.1
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
T1/2 is the terminal elimination half-life, which is estimated by Loge(2) / kel, where kel is the apparent terminal elimination rate constant. 5-OH Omeprazole was the metabolite of omeprazole.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
T1/2 of Plasma 5-OH Omeprazole on Day -7, Day 1 and Day 14
Day -7
|
2.29 Hours
Geometric Coefficient of Variation 43.1
|
—
|
—
|
|
T1/2 of Plasma 5-OH Omeprazole on Day -7, Day 1 and Day 14
Day 1
|
3.53 Hours
Geometric Coefficient of Variation 45.7
|
—
|
—
|
|
T1/2 of Plasma 5-OH Omeprazole on Day -7, Day 1 and Day 14
Day 14
|
1.80 Hours
Geometric Coefficient of Variation 22.5
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 2 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 2 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
T1/2 is the terminal elimination half-life, which is estimated by Loge(2) / kel, where kel is the apparent terminal elimination rate constant.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=10 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
T1/2 of Plasma Rosuvastatin on Day -7, Day 1 and Day 14
Day -7
|
3.25 Hours
Geometric Coefficient of Variation 51.8
|
—
|
—
|
|
T1/2 of Plasma Rosuvastatin on Day -7, Day 1 and Day 14
Day 1
|
2.13 Hours
Geometric Coefficient of Variation 17.0
|
—
|
—
|
|
T1/2 of Plasma Rosuvastatin on Day -7, Day 1 and Day 14
Day 14
|
1.86 Hours
Geometric Coefficient of Variation 23.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 2 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 2 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
T1/2 is the terminal elimination half-life, which is estimated by Loge(2) / kel, where kel is the apparent terminal elimination rate constant.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=10 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
T1/2 of Plasma Bupropion on Day -7, Day 1 and Day 14
Day -7
|
2.81 Hours
Geometric Coefficient of Variation 15.1
|
—
|
—
|
|
T1/2 of Plasma Bupropion on Day -7, Day 1 and Day 14
Day 1
|
3.24 Hours
Geometric Coefficient of Variation 10.2
|
—
|
—
|
|
T1/2 of Plasma Bupropion on Day -7, Day 1 and Day 14
Day 14
|
2.75 Hours
Geometric Coefficient of Variation 15.2
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
CL/F is the apparent total body clearance of drug from the plasma (parent drugs only), which is estimated by Dose / AUCinf (Day -7) or Dose / AUClast (Day 1 and Day 14).
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Apparent Clearance (CL/F) of Plasma Midazolam on Day -7, Day 1 and Day 14
Day -7
|
73.9 Liters (L)/hour (h)
Geometric Coefficient of Variation 72.5
|
—
|
—
|
|
Apparent Clearance (CL/F) of Plasma Midazolam on Day -7, Day 1 and Day 14
Day 1
|
73.9 Liters (L)/hour (h)
Geometric Coefficient of Variation 65.1
|
—
|
—
|
|
Apparent Clearance (CL/F) of Plasma Midazolam on Day -7, Day 1 and Day 14
Day 14
|
392 Liters (L)/hour (h)
Geometric Coefficient of Variation 52.5
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
CL/F is the apparent total body clearance of drug from the plasma (parent drugs only), which is estimated by Dose / AUCinf (Day -7) or Dose / AUClast (Day 1 and Day 14).
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
CL/F of Plasma Omeprazole on Day -7, Day 1 and Day 14
Day -7
|
12.3 L/h
Geometric Coefficient of Variation 151.6
|
—
|
—
|
|
CL/F of Plasma Omeprazole on Day -7, Day 1 and Day 14
Day 1
|
17.0 L/h
Geometric Coefficient of Variation 79.4
|
—
|
—
|
|
CL/F of Plasma Omeprazole on Day -7, Day 1 and Day 14
Day 14
|
22.1 L/h
Geometric Coefficient of Variation 35.7
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
Vz/F is the apparent volume of distribution during the terminal phase (parent drugs only), which is calculated by CL/F/kel.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Apparent Total Volume of Distribution Following Oral Administration (Vz/F) of Plasma Midazolam on Day -7, Day 1 and Day 14
Day -7
|
306 Litre
Geometric Coefficient of Variation 67.7
|
—
|
—
|
|
Apparent Total Volume of Distribution Following Oral Administration (Vz/F) of Plasma Midazolam on Day -7, Day 1 and Day 14
Day 1
|
339 Litre
Geometric Coefficient of Variation 54.6
|
—
|
—
|
|
Apparent Total Volume of Distribution Following Oral Administration (Vz/F) of Plasma Midazolam on Day -7, Day 1 and Day 14
Day 14
|
1030 Litre
Geometric Coefficient of Variation 54.7
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
Vz/F is the apparent volume of distribution during the terminal phase (parent drugs only), which is calculated by CL/F/kel.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Vz/F of Plasma Omeprazole on Day -7, Day 1 and Day 14
Day -7
|
29.1 Litre
Geometric Coefficient of Variation 93.9
|
—
|
—
|
|
Vz/F of Plasma Omeprazole on Day -7, Day 1 and Day 14
Day 1
|
44.6 Litre
Geometric Coefficient of Variation 63.7
|
—
|
—
|
|
Vz/F of Plasma Omeprazole on Day -7, Day 1 and Day 14
Day 14
|
45.9 Litre
Geometric Coefficient of Variation 39.3
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 0 to 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
Fe is the percentage of dose recovered in urine from 0 to 8 hours as parent or metabolite, which was calculated as Ae0-8 / dose × 100.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Percentage of Dose Recovered in Urine (Fe) for Losartan on Day -7, Day 1 and Day 14
Day -7
|
0.478 Percentage of dose
Geometric Coefficient of Variation 268.0
|
—
|
—
|
|
Percentage of Dose Recovered in Urine (Fe) for Losartan on Day -7, Day 1 and Day 14
Day 1
|
0.699 Percentage of dose
Geometric Coefficient of Variation 314.2
|
—
|
—
|
|
Percentage of Dose Recovered in Urine (Fe) for Losartan on Day -7, Day 1 and Day 14
Day 14
|
0.572 Percentage of dose
Geometric Coefficient of Variation 277.3
|
—
|
—
|
SECONDARY outcome
Timeframe: 0 to 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
Fe is the percentage of dose recovered in urine from 0 to 8 hours as parent or metabolite, which was calculated as Ae0-8 / dose × 100. E-3174 was the metabolite of losartan.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Fe for E-3174 on Day -7, Day 1 and Day 14
Day -7
|
0.440 Percentage of dose
Geometric Coefficient of Variation 293.3
|
—
|
—
|
|
Fe for E-3174 on Day -7, Day 1 and Day 14
Day 1
|
0.644 Percentage of dose
Geometric Coefficient of Variation 276.2
|
—
|
—
|
|
Fe for E-3174 on Day -7, Day 1 and Day 14
Day 14
|
0.396 Percentage of dose
Geometric Coefficient of Variation 317.8
|
—
|
—
|
SECONDARY outcome
Timeframe: 0 to 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
Fe is the percentage of dose recovered in urine from 0 to 8 hours as parent or metabolite, which was calculated as Ae0-8 / dose × 100.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Fe for Dextromethorphan on Day -7, Day 1 and Day 14
Day -7
|
0.0881 Percentage of dose
Geometric Coefficient of Variation 396.7
|
—
|
—
|
|
Fe for Dextromethorphan on Day -7, Day 1 and Day 14
Day 1
|
0.108 Percentage of dose
Geometric Coefficient of Variation 542.5
|
—
|
—
|
|
Fe for Dextromethorphan on Day -7, Day 1 and Day 14
Day 14
|
0.0750 Percentage of dose
Geometric Coefficient of Variation 899.2
|
—
|
—
|
SECONDARY outcome
Timeframe: 0 to 8 hours postdose on Day -7, Day 1 and Day 14Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
Fe is the percentage of dose recovered in urine from 0 to 8 hours as parent or metabolite, which was calculated as Ae0-8 / dose × 100. Dextrorphan was the metabolite of dextromethorphan.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Fe for Dextrorphan on Day -7, Day 1 and Day 14
Day -7
|
13.3 Percentage of dose
Geometric Coefficient of Variation 183.9
|
—
|
—
|
|
Fe for Dextrorphan on Day -7, Day 1 and Day 14
Day 1
|
15.6 Percentage of dose
Geometric Coefficient of Variation 165.5
|
—
|
—
|
|
Fe for Dextrorphan on Day -7, Day 1 and Day 14
Day 14
|
12.5 Percentage of dose
Geometric Coefficient of Variation 222.5
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1 and Day 14.Population: All participants in Arms 1 and 2 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days 1 and 14. Number of participants analyzed represents the total number of participants in each arm in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
Cmax is the maximum plasma concentration which was observed directly from the concentration-time data.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=20 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
n=10 Participants
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Cmax of Encorafenib on Day 1 and Day 14
Day 1
|
6150 ng/mL
Geometric Coefficient of Variation 41.9
|
6060 ng/mL
Geometric Coefficient of Variation 77.7
|
—
|
|
Cmax of Encorafenib on Day 1 and Day 14
Day 14
|
3240 ng/mL
Geometric Coefficient of Variation 55.7
|
2940 ng/mL
Geometric Coefficient of Variation 72.2
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1 and Day 14Population: All participants in Arms 1 and 2 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days 1 and 14. Number of participants analyzed represents the total number of participants in each arm in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
Cmax is the maximum plasma concentration which was observed directly from the concentration-time data. LHY746 was the metabolite of encorafenib.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=20 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
n=10 Participants
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Cmax of LHY746 on Day 1 and Day 14
Day 1
|
943 ng/mL
Geometric Coefficient of Variation 66.6
|
953 ng/mL
Geometric Coefficient of Variation 66.0
|
—
|
|
Cmax of LHY746 on Day 1 and Day 14
Day 14
|
2490 ng/mL
Geometric Coefficient of Variation 32.4
|
2340 ng/mL
Geometric Coefficient of Variation 66.8
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1 and Day 14.Population: All participants in Arms 1 and 2 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days 1 and 14. Number of participants analyzed represents the total number of participants in each arm in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
Cmax is the maximum plasma concentration which was observed directly from the concentration-time data.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=20 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
n=10 Participants
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Cmax of Binimetinib on Day 1 and Day 14
Day 1
|
661 ng/mL
Geometric Coefficient of Variation 55.1
|
549 ng/mL
Geometric Coefficient of Variation 89.5
|
—
|
|
Cmax of Binimetinib on Day 1 and Day 14
Day 14
|
521 ng/mL
Geometric Coefficient of Variation 59.9
|
566 ng/mL
Geometric Coefficient of Variation 63.1
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1 and Day 14Population: All participants in Arms 1 and 2 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days 1 and 14. Number of participants analyzed represents the total number of participants in each arm in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
Cmax is the maximum plasma concentration which was observed directly from the concentration-time data. AR00426032 was the metabolite of binimetinib.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=20 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
n=10 Participants
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Cmax of AR00426032 on Day 1 and Day 14
Day 1
|
57.0 ng/mL
Geometric Coefficient of Variation 41.2
|
63.3 ng/mL
Geometric Coefficient of Variation 73.2
|
—
|
|
Cmax of AR00426032 on Day 1 and Day 14
Day 14
|
23.3 ng/mL
Geometric Coefficient of Variation 85.6
|
27.4 ng/mL
Geometric Coefficient of Variation 43.1
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1 and Day 14.Population: All participants in Arms 1 and 2 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days 1 and 14. Number of participants analyzed represents the total number of participants in each arm in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
AUClast is AUC from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=20 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
n=10 Participants
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
AUClast of Encorafenib on Day 1 and Day 14
Day 1
|
24500 ng*hr/mL
Geometric Coefficient of Variation 36.7
|
25900 ng*hr/mL
Geometric Coefficient of Variation 61.7
|
—
|
|
AUClast of Encorafenib on Day 1 and Day 14
Day 14
|
12700 ng*hr/mL
Geometric Coefficient of Variation 37.6
|
13100 ng*hr/mL
Geometric Coefficient of Variation 28.6
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1 and Day 14Population: All participants in Arms 1 and 2 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days 1 and 14. Number of participants analyzed represents the total number of participants in each arm in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
AUClast is AUC from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method. LHY746 was the metabolite of encorafenib.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=20 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
n=10 Participants
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
AUClast of LHY746 on Day 1 and Day 14
Day 1
|
5130 ng*hr/mL
Geometric Coefficient of Variation 66.1
|
4990 ng*hr/mL
Geometric Coefficient of Variation 78.1
|
—
|
|
AUClast of LHY746 on Day 1 and Day 14
Day 14
|
34000 ng*hr/mL
Geometric Coefficient of Variation 34.4
|
32800 ng*hr/mL
Geometric Coefficient of Variation 54.5
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1 and Day 14Population: All participants in Arms 1 and 2 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days 1 and 14. Number of participants analyzed represents the total number of participants in each arm in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
AUClast is AUC from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=20 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
n=10 Participants
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
AUClast of Binimetinib on Day 1 and Day 14
Day 1
|
2290 ng*hr/mL
Geometric Coefficient of Variation 43.3
|
2040 ng*hr/mL
Geometric Coefficient of Variation 81.0
|
—
|
|
AUClast of Binimetinib on Day 1 and Day 14
Day 14
|
2190 ng*hr/mL
Geometric Coefficient of Variation 33.8
|
2210 ng*hr/mL
Geometric Coefficient of Variation 40.7
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1 and Day 14Population: All participants in Arms 1 and 2 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days 1 and 14. Number of participants analyzed represents the total number of participants in each arm in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
AUClast is AUC from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method. AR00426032 was the metabolite of binimetinib.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=20 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
n=10 Participants
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
AUClast of AR00426032 on Day 1 and Day 14
Day 1
|
236 ng*hr/mL
Geometric Coefficient of Variation 39.6
|
256 ng*hr/mL
Geometric Coefficient of Variation 74.8
|
—
|
|
AUClast of AR00426032 on Day 1 and Day 14
Day 14
|
108 ng*hr/mL
Geometric Coefficient of Variation 74.1
|
122 ng*hr/mL
Geometric Coefficient of Variation 67.4
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1 and Day 14.Population: All participants in Arms 1 and 2 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days 1 and 14. Number of participants analyzed represents the total number of participants in each arm in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
Tmax is time to reach maximum observed plasma concentration. It was observed directly from the concentration-time data.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=20 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
n=10 Participants
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Tmax of Encorafenib on Day 1 and Day 14
Day 1
|
2.00 Hours
Interval 1.0 to 5.92
|
1.87 Hours
Interval 0.85 to 3.98
|
—
|
|
Tmax of Encorafenib on Day 1 and Day 14
Day 14
|
1.94 Hours
Interval 0.82 to 3.02
|
1.93 Hours
Interval 1.0 to 4.0
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours (+/- 15 minutes window for each time-point) postdose on Day 1 and Day 14Population: All participants in Arms 1 and 2 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days 1 and 14. Number of participants analyzed represents the total number of participants in each arm in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
Tmax is time to reach maximum observed plasma concentration. It was observed directly from the concentration-time data. LHY746 was the metabolite of encorafenib.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=20 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
n=10 Participants
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Tmax of LHY746 on Day 1 and Day 14
Day 1
|
6.93 Hours
Interval 2.07 to 8.07
|
7.42 Hours
Interval 3.0 to 8.0
|
—
|
|
Tmax of LHY746 on Day 1 and Day 14
Day 14
|
2.98 Hours
Interval 1.8 to 8.22
|
3.47 Hours
Interval 1.85 to 6.25
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1 and Day 14.Population: All participants in Arms 1 and 2 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days 1 and 14. Number of participants analyzed represents the total number of participants in each arm in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
Tmax is time to reach maximum observed plasma concentration. It was observed directly from the concentration-time data.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=20 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
n=10 Participants
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Tmax of Binimetinib on Day 1 and Day 14
Day 1
|
1.97 Hours
Interval 0.87 to 4.03
|
1.97 Hours
Interval 0.85 to 4.08
|
—
|
|
Tmax of Binimetinib on Day 1 and Day 14
Day 14
|
1.98 Hours
Interval 0.97 to 3.02
|
1.93 Hours
Interval 1.02 to 2.92
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1 and Day 14Population: All participants in Arms 1 and 2 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days 1 and 14. Number of participants analyzed represents the total number of participants in each arm in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
Tmax is time to reach maximum observed plasma concentration. It was observed directly from the concentration-time data. AR00426032 was the metabolite of binimetinib.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=20 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
n=10 Participants
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Tmax of AR00426032 on Day 1 and Day 14
Day 1
|
2.02 Hours
Interval 0.98 to 4.03
|
2.48 Hours
Interval 1.82 to 6.13
|
—
|
|
Tmax of AR00426032 on Day 1 and Day 14
Day 14
|
2.00 Hours
Interval 0.98 to 3.02
|
2.00 Hours
Interval 1.0 to 2.92
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1Population: All participants in Arms 1 and 2 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Day 1. Number of participants analyzed represents the number of participants who had reportable parameter values.
AUCinf is AUC from time zero to extrapolated infinite time. It is obtained by AUClast + (Clast/kel), where AUClast is the AUC from time zero to the time of last quantifiable concentration (Clast), and kel is the apparent terminal elimination rate constant.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=4 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
n=3 Participants
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
AUCinf of Encorafenib on Day 1
|
26200 ng*hr/mL
Geometric Coefficient of Variation 71.6
|
45100 ng*hr/mL
Geometric Coefficient of Variation 56.8
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1.Population: All participants in Arms 1 and 2 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Day 1. Number of participants analyzed represents the number of participants who had reportable parameter values.
AUCinf is AUC from time zero to extrapolated infinite time. It is obtained by AUClast + (Clast/kel), where AUClast is the AUC from time zero to the time of last quantifiable concentration (Clast), and kel is the apparent terminal elimination rate constant.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=12 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
n=6 Participants
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
AUCinf of Binimetinib on Day 1
|
2970 ng*hr/mL
Geometric Coefficient of Variation 45.4
|
3280 ng*hr/mL
Geometric Coefficient of Variation 47.7
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1Population: All participants in Arms 1 and 2 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Day 1. Number of participants analyzed represents the total number of participants in each arm in the evaluable PK set. Number of analyzed represents the number of participants who had reportable parameter values.
AUCinf is AUC from time zero to extrapolated infinite time. It is obtained by AUClast + (Clast/kel), where AUClast is the AUC from time zero to the time of last quantifiable concentration (Clast), and kel is the apparent terminal elimination rate constant.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=9 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
n=2 Participants
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
AUCinf of AR00426032 on Day 1
|
270 ng*hr/mL
Geometric Coefficient of Variation 40.5
|
432 ng*hr/mL
Geometric Coefficient of Variation 32.4
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1 and Day 14Population: All participants in Arms 1 and 2 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days 1 and 14. Number of participants analyzed represents the total number of participants in each arm in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
T1/2 is the terminal elimination half-life, which is estimated by Loge(2) / kel, where kel is the apparent terminal elimination rate constant.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=20 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
n=10 Participants
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
T1/2 of Encorafenib on Day 1 and Day 14
Day 1
|
3.98 Hours
Geometric Coefficient of Variation 46.4
|
3.77 Hours
Geometric Coefficient of Variation 37.0
|
—
|
|
T1/2 of Encorafenib on Day 1 and Day 14
Day 14
|
4.37 Hours
Geometric Coefficient of Variation 42.7
|
3.58 Hours
Geometric Coefficient of Variation 13.7
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1 and Day 14Population: All participants in Arms 1 and 2 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days 1 and 14. Number of participants analyzed represents the total number of participants in each arm in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
T1/2 is the terminal elimination half-life, which is estimated by Loge(2) / kel, where kel is the apparent terminal elimination rate constant. LHY746 was the metabolite of encorafenib.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=20 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
n=10 Participants
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
T1/2 of LHY746 on Day 1 and Day 14
Day 1
|
9.47 Hours
Geometric Coefficient of Variation 130.1
|
22.5 Hours
Geometric Coefficient of Variation NA
Data was not reported as only 1 participant was analyzed for this arm.
|
—
|
|
T1/2 of LHY746 on Day 1 and Day 14
Day 14
|
9.27 Hours
Geometric Coefficient of Variation 40.0
|
11.2 Hours
Geometric Coefficient of Variation 20.6
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1 and Day 14Population: All participants in Arms 1 and 2 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days 1 and 14. Number of participants analyzed represents the total number of participants in each arm in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
T1/2 is the terminal elimination half-life, which is estimated by Loge(2) / kel, where kel is the apparent terminal elimination rate constant.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=20 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
n=10 Participants
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
T1/2 of Binimetinib on Day 1 and Day 14
Day 1
|
2.62 Hours
Geometric Coefficient of Variation 35.4
|
2.45 Hours
Geometric Coefficient of Variation 17.3
|
—
|
|
T1/2 of Binimetinib on Day 1 and Day 14
Day 14
|
3.90 Hours
Geometric Coefficient of Variation 39.9
|
3.70 Hours
Geometric Coefficient of Variation 42.8
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1 and Day 14Population: All participants in Arms 1 and 2 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days 1 and 14. Number of participants analyzed represents the total number of participants in each arm in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
T1/2 is the terminal elimination half-life, which is estimated by Loge(2) / kel, where kel is the apparent terminal elimination rate constant. AR00426032 was the metabolite of binimetinib.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=20 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
n=10 Participants
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
T1/2 of AR00426032 on Day 1 and Day 14
Day 1
|
2.96 Hours
Geometric Coefficient of Variation 23.3
|
3.15 Hours
Geometric Coefficient of Variation 24.7
|
—
|
|
T1/2 of AR00426032 on Day 1 and Day 14
Day 14
|
3.97 Hours
Geometric Coefficient of Variation 42.6
|
3.89 Hours
Geometric Coefficient of Variation 51.9
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Day 1. Number of participants analyzed represents the number of participants who had reportable parameter values.
AUC%extrap is the percentage of AUCinf obtained by forward extrapolation. It is calculated as (AUCinf minus AUClast)\*100/ AUCinf.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
AUC%Extrap of Encorafenib on Day 1
|
24.4 Percentage of AUC
Geometric Coefficient of Variation 73.9
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Day 1. Number of participants analyzed represents the number of participants who had reportable parameter values.
AUC%extrap is the percentage of AUCinf obtained by forward extrapolation. It is calculated as (AUCinf minus AUClast)\*100/ AUCinf. LHY746 was the metabolite of encorafenib.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=2 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
AUC%Extrap of LHY746 on Day 1
|
52.9 Percentage of AUC
Geometric Coefficient of Variation 56.1
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Day 1. Number of participants analyzed represents the number of participants who had reportable parameter values.
AUC%extrap is the percentage of AUCinf obtained by forward extrapolation. It is calculated as (AUCinf minus AUClast)\*100/ AUCinf.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=17 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
AUC%Extrap of Binimetinib on Day 1
|
13.7 Percentage of AUC
Geometric Coefficient of Variation 60.2
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Day 1. Number of participants analyzed represents the number of participants who had reportable parameter values.
AUC%extrap is the percentage of AUCinf obtained by forward extrapolation. It is calculated as (AUCinf minus AUClast)\*100/ AUCinf. AR00426032 was the metabolite of binimetinib.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=17 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
AUC%Extrap of AR00426032 on Day 1
|
19.8 Percentage of AUC
Geometric Coefficient of Variation 33.8
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Day 1. Number of participants analyzed represents the number of participants who had reportable parameter values.
Kel is the apparent terminal elimination rate constant, which is estimated by linear regression of time versus loge concentration.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=19 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Kel of Encorafenib on Day 1
|
0.174 Fraction/hour
Geometric Coefficient of Variation 46.4
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Day 1. Number of participants analyzed represents the number of participants who had reportable parameter values.
Kel is the apparent terminal elimination rate constant, which is estimated by linear regression of time versus loge concentration. LHY746 was the metabolite of encorafenib.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=2 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Kel of LHY746 on Day 1
|
0.0732 Fraction/hour
Geometric Coefficient of Variation 130.1
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Day 1. Number of participants analyzed represents the number of participants who had reportable parameter values.
Kel is the apparent terminal elimination rate constant, which is estimated by linear regression of time versus loge concentration.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=17 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Kel of Binimetinib on Day 1
|
0.265 Fraction/hour
Geometric Coefficient of Variation 35.4
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Day 1. Number of participants analyzed represents the number of participants who had reportable parameter values.
Kel is the apparent terminal elimination rate constant, which is estimated by linear regression of time versus loge concentration. AR00426032 was the metabolite of binimetinib.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=17 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Kel of AR00426032 on Day 1
|
0.234 Fraction/hour
Geometric Coefficient of Variation 23.3
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1.Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Day 1. Number of participants analyzed represents the number of participants who had reportable parameter values.
CL/F is the apparent total body clearance of drug from the plasma (parent drugs only), which is estimated by Dose / AUCinf (Day -7) or Dose / AUClast (Day 1 and Day 14).
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=4 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
CL/F of Encorafenib on Day 1
|
17.2 L/h
Geometric Coefficient of Variation 71.6
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1.Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Day 1. Number of participants analyzed represents the number of participants who had reportable parameter values.
CL/F is the apparent total body clearance of drug from the plasma (parent drugs only), which is estimated by Dose / AUCinf (Day -7) or Dose / AUClast (Day 1 and Day 14).
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=12 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
CL/F of Binimetinib on Day 1
|
15.1 L/h
Geometric Coefficient of Variation 45.4
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1.Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Day 1. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number of analyzed represents the number of participants who had reportable parameter values.
Vz/F is the apparent volume of distribution during the terminal phase (parent drugs only), which is calculated by CL/F/kel.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=4 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Vz/F of Encorafenib on Day 1
|
53.4 Litre
Geometric Coefficient of Variation 38.2
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1.Population: All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Day 1. Number of participants analyzed represents the number of participants who had reportable parameter values.
Vz/F is the apparent volume of distribution during the terminal phase (parent drugs only), which is calculated by CL/F/kel.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=12 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Vz/F of Binimetinib on Day 1
|
47.6 Litre
Geometric Coefficient of Variation 50.5
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21Population: All participants in Arm 3 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days 14 and 21. Number of participants analyzed represents the total number of participants in Arm 3 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
Cmax is the maximum plasma concentration which was observed directly from the concentration-time data.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=11 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Cmax of Binimetinib on Day 14 and Day 21
Day 14
|
660 ng/mL
Geometric Coefficient of Variation 39.7
|
—
|
—
|
|
Cmax of Binimetinib on Day 14 and Day 21
Day 21
|
663 ng/mL
Geometric Coefficient of Variation 25.3
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21Population: All participants in Arm 3 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days 14 and 21. Number of participants analyzed represents the total number of participants in Arm 3 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
Cmax is the maximum plasma concentration which was observed directly from the concentration-time data. AR00426032 was the metabolite of binimetinib.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=11 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Cmax of AR00426032 on Day 14 and Day 21
Day 14
|
25.9 ng/mL
Geometric Coefficient of Variation 63.2
|
—
|
—
|
|
Cmax of AR00426032 on Day 14 and Day 21
Day 21
|
24.7 ng/mL
Geometric Coefficient of Variation 36.7
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21Population: All participants in Arm 3 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days 14 and 21. Number of participants analyzed represents the total number of participants in Arm 3 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
AUClast is AUC from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=11 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
AUClast of Binimetinib on Day 14 and Day 21
Day 14
|
2400 ng*hr/mL
Geometric Coefficient of Variation 38.6
|
—
|
—
|
|
AUClast of Binimetinib on Day 14 and Day 21
Day 21
|
2290 ng*hr/mL
Geometric Coefficient of Variation 30.6
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21Population: All participants in Arm 3 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days 14 and 21. Number of participants analyzed represents the total number of participants in Arm 3 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
AUClast is AUC from time 0 (pre-dose) to the time of the last quantifiable concentration. AR00426032 was the metabolite of binimetinib.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=11 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
AUClast of AR00426032 on Day 14 and Day 21
Day 14
|
114 ng*hr/mL
Geometric Coefficient of Variation 64.5
|
—
|
—
|
|
AUClast of AR00426032 on Day 14 and Day 21
Day 21
|
112 ng*hr/mL
Geometric Coefficient of Variation 33.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21Population: All participants in Arm 3 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days 14 and 21. Number of participants analyzed represents the total number of participants in Arm 3 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
Tmax is time to reach maximum observed plasma concentration. It was observed directly from the concentration-time data.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=11 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Tmax of Encorafenib on Day 14 and Day 21
Day 14
|
1.00 Hours
Interval 0.88 to 2.03
|
—
|
—
|
|
Tmax of Encorafenib on Day 14 and Day 21
Day 21
|
1.00 Hours
Interval 0.98 to 3.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21Population: All participants in Arm 3 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days 14 and 21. Number of participants analyzed represents the total number of participants in Arm 3 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
Tmax is time to reach maximum observed plasma concentration. It was observed directly from the concentration-time data. LHY746 was the metabolite of encorafenib.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=11 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Tmax of LHY746 on Day 14 and Day 21
Day 14
|
2.05 Hours
Interval 1.0 to 6.0
|
—
|
—
|
|
Tmax of LHY746 on Day 14 and Day 21
Day 21
|
2.10 Hours
Interval 1.0 to 6.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21Population: All participants in Arm 3 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days 14 and 21. Number of participants analyzed represents the total number of participants in Arm 3 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
Tmax is time to reach maximum observed plasma concentration. It was observed directly from the concentration-time data.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=11 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Tmax of Binimetinib on Day 14 and Day 21
Day 14
|
1.00 Hours
Interval 0.88 to 3.0
|
—
|
—
|
|
Tmax of Binimetinib on Day 14 and Day 21
Day 21
|
1.00 Hours
Interval 0.95 to 2.1
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21Population: All participants in Arm 3 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days 14 and 21. Number of participants analyzed represents the total number of participants in Arm 3 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
Tmax is time to reach maximum observed plasma concentration. It was observed directly from the concentration-time data. AR00426032 was the metabolite of binimetinib.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=11 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Tmax of AR00426032 on Day 14 and Day 21
Day 14
|
2.00 Hours
Interval 0.88 to 3.0
|
—
|
—
|
|
Tmax of AR00426032 on Day 14 and Day 21
Day 21
|
2.00 Hours
Interval 0.95 to 2.23
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21Population: All participants in Arm 3 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days 14 and 21. Number of participants analyzed represents the total number of participants in Arm 3 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
T1/2 is the terminal elimination half-life, which is estimated by Loge(2) / kel, where kel is the apparent terminal elimination rate constant.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=11 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
T1/2 of Encorafenib on Day 14 and Day 21
Day 14
|
3.48 Hours
Geometric Coefficient of Variation 26.6
|
—
|
—
|
|
T1/2 of Encorafenib on Day 14 and Day 21
Day 21
|
3.57 Hours
Geometric Coefficient of Variation 27.3
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21Population: All participants in Arm 3 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days 14 and 21. Number of participants analyzed represents the total number of participants in Arm 3 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
T1/2 is the terminal elimination half-life, which is estimated by Loge(2) / kel, where kel is the apparent terminal elimination rate constant. LHY746 was the metabolite of encorafenib.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=11 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
T1/2 of LHY746 on Day 14 and Day 21
Day 14
|
8.67 Hours
Geometric Coefficient of Variation 33.1
|
—
|
—
|
|
T1/2 of LHY746 on Day 14 and Day 21
Day 21
|
8.01 Hours
Geometric Coefficient of Variation 18.8
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21Population: All participants in Arm 3 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days 14 and 21. Number of participants analyzed represents the total number of participants in Arm 3 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
T1/2 is the terminal elimination half-life, which is estimated by Loge(2) / kel, where kel is the apparent terminal elimination rate constant.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=11 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
T1/2 of Binimetinib on Day 14 and Day 21
Day 14
|
4.62 Hours
Geometric Coefficient of Variation 42.1
|
—
|
—
|
|
T1/2 of Binimetinib on Day 14 and Day 21
Day 21
|
4.55 Hours
Geometric Coefficient of Variation 44.8
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21Population: All participants in Arm 3 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days 14 and 21. Number of participants analyzed represents the total number of participants in Arm 3 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.
T1/2 is the terminal elimination half-life, which is estimated by Loge(2) / kel, where kel is the apparent terminal elimination rate constant. AR00426032 was the metabolite of binimetinib.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=11 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
T1/2 of AR00426032 on Day 14 and Day 21
Day 14
|
5.60 Hours
Geometric Coefficient of Variation 37.1
|
—
|
—
|
|
T1/2 of AR00426032 on Day 14 and Day 21
Day 21
|
5.22 Hours
Geometric Coefficient of Variation 58.7
|
—
|
—
|
SECONDARY outcome
Timeframe: After 1st dose of encorafenib/binimetinib on Day 1 and up to Day 28 visit in the DDI PhasePopulation: All participants who received at least 1 dose of encorafenib/binimetinib.
An adverse event (AE) was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were those with initial onset or increasing in severity between the first dose of encorafenib/binimetinib and up to 30 days after treatment discontinuation. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. SAEs were adjudicated according to the investigator's assessment. Treatment-related AEs and SAEs were determined by the investigator.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=27 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
n=12 Participants
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
n=15 Participants
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the DDI Phase
Participants with treatment-related TEAEs
|
24 Count of Participants
|
6 Count of Participants
|
10 Count of Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the DDI Phase
AEs requiring dose reduction (treatment-related)
|
2 Count of Participants
|
2 Count of Participants
|
0 Count of Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the DDI Phase
AEs requiring additional therapy (treatment-related)
|
8 Count of Participants
|
6 Count of Participants
|
8 Count of Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the DDI Phase
Deaths
|
0 Count of Participants
|
0 Count of Participants
|
0 Count of Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the DDI Phase
Participants with all-causality TEAEs
|
26 Count of Participants
|
9 Count of Participants
|
11 Count of Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the DDI Phase
Participants with all-causality SAEs
|
2 Count of Participants
|
1 Count of Participants
|
0 Count of Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the DDI Phase
Participants with treatment-related SAEs
|
1 Count of Participants
|
1 Count of Participants
|
0 Count of Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the DDI Phase
AEs leading to study drug discontinuation (all-causality)
|
3 Count of Participants
|
2 Count of Participants
|
0 Count of Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the DDI Phase
AEs leading to study drug discontinuation (treatment-related)
|
2 Count of Participants
|
2 Count of Participants
|
0 Count of Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the DDI Phase
AEs requiring dose interruption (all-causality)
|
10 Count of Participants
|
4 Count of Participants
|
4 Count of Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the DDI Phase
AEs requiring dose interruption (treatment-related)
|
8 Count of Participants
|
2 Count of Participants
|
2 Count of Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the DDI Phase
AEs requiring dose reduction (all-causality)
|
2 Count of Participants
|
2 Count of Participants
|
0 Count of Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the DDI Phase
AEs requiring additional therapy (all-causality)
|
13 Count of Participants
|
8 Count of Participants
|
10 Count of Participants
|
SECONDARY outcome
Timeframe: After 1st dose of encorafenib/binimetinib on Day 1 and up to Day 28 visit in the DDI PhasePopulation: All participants who received at least 1 dose of encorafenib/binimetinib.
Laboratory parameters:hematology (hemoglobin,hematocrit,red blood cell \[RBC\],platelet,white blood cell count \[WBC\],neutrophils,eosinophils,monocytes, basophils, lymphocytes), chemistry (albumin, alkaline phosphatase, alanine aminotransferase, amylase, aspartate aminotransferase, bicarbonate, total bilirubin, blood urea nitrogen, calcium, chloride, creatine kinase, creatinine, glucose, lactate dehydrogenase, lipase, magnesium, inorganic phosphate, potassium, total protein, sodium, uric acid), urinalysis (appearance, color, specific gravity, pH, ketones, protein, glucose, blood, nitrates, leukocyte esterase, and urine microscopy results including WBC, RBC, bacteria, epithelial cells, and casts), coagulation (activated partial thromboplastin time, prothrombin time/international normalized ratio) and others. Clinically notable: worsening from baseline by at least 2 grades or to greater than or equal to (\>=) Grade 3, by Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=27 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
n=12 Participants
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
n=15 Participants
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Number of Participants With Laboratory Abnormalities in the DDI Phase
Hemoglobin CTCAE Graded Low
|
0 Count of Participants
|
1 Count of Participants
|
0 Count of Participants
|
|
Number of Participants With Laboratory Abnormalities in the DDI Phase
Lymphocytes CTCAE Graded Low
|
3 Count of Participants
|
2 Count of Participants
|
0 Count of Participants
|
|
Number of Participants With Laboratory Abnormalities in the DDI Phase
Lymphocytes CTCAE Graded High
|
2 Count of Participants
|
0 Count of Participants
|
0 Count of Participants
|
|
Number of Participants With Laboratory Abnormalities in the DDI Phase
Neutrophils CTCAE Graded Low
|
2 Count of Participants
|
1 Count of Participants
|
0 Count of Participants
|
|
Number of Participants With Laboratory Abnormalities in the DDI Phase
Amylase CTCAE Graded High
|
2 Count of Participants
|
0 Count of Participants
|
1 Count of Participants
|
|
Number of Participants With Laboratory Abnormalities in the DDI Phase
Lipase CTCAE Graded High
|
7 Count of Participants
|
0 Count of Participants
|
0 Count of Participants
|
|
Number of Participants With Laboratory Abnormalities in the DDI Phase
Glucose CTCAE Graded Low
|
0 Count of Participants
|
1 Count of Participants
|
1 Count of Participants
|
|
Number of Participants With Laboratory Abnormalities in the DDI Phase
Creatine Kinase CTCAE Graded High
|
0 Count of Participants
|
2 Count of Participants
|
0 Count of Participants
|
|
Number of Participants With Laboratory Abnormalities in the DDI Phase
Creatinine CTCAE Graded High
|
2 Count of Participants
|
0 Count of Participants
|
3 Count of Participants
|
|
Number of Participants With Laboratory Abnormalities in the DDI Phase
Glucose CTCAE Graded High
|
2 Count of Participants
|
1 Count of Participants
|
1 Count of Participants
|
SECONDARY outcome
Timeframe: After 1st dose of encorafenib/binimetinib on Day 1 and up to Day 28 visit in the DDI PhasePopulation: All participants who received at least 1 dose of encorafenib/binimetinib.
Vital signs (temperature, pulse rate \[PR\]), systolic blood pressure \[SBP\]), and diastolic blood pressure \[DBP\]) were obtained with participants following at least 5 minutes of supine rest. Categorical criteria were defined as DBP\>=100 millimeters of mercury (mm Hg)/less than or equal to (\<=) 50 mmHg with increase/decrease from baseline of \>=15 mmHg; SBP: \>=160 mmHg/\<=90 mmHg with increase/decrease from baseline of \>=20 mmHg; PR: \>=120 beats per minute (bpm)/\<=50 bpm with increase/decrease from baseline of \>=15 bpm; temperature for Arms 1 and 3: \>=37.5°C/\<=35°C; Arms 2: \>=37.5°C/\<=36°C.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=27 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
n=12 Participants
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
n=15 Participants
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Number of Participants With Notable Abnormalities in Vital Signs in the DDI Phase
SBP high (>=160mmHg with increase from baseline of >=20mmHg)
|
4 Count of Participants
|
4 Count of Participants
|
0 Count of Participants
|
|
Number of Participants With Notable Abnormalities in Vital Signs in the DDI Phase
SBP low (<=90mmHg with decrease from baseline of >=20mmHg)
|
0 Count of Participants
|
0 Count of Participants
|
1 Count of Participants
|
|
Number of Participants With Notable Abnormalities in Vital Signs in the DDI Phase
DBP high (>=100mmHg with increase from baseline of >=15mmHg)
|
1 Count of Participants
|
0 Count of Participants
|
0 Count of Participants
|
|
Number of Participants With Notable Abnormalities in Vital Signs in the DDI Phase
PR high (>=120bpm with increase from baseline of >=15bpm)
|
1 Count of Participants
|
1 Count of Participants
|
0 Count of Participants
|
|
Number of Participants With Notable Abnormalities in Vital Signs in the DDI Phase
Temperature high
|
0 Count of Participants
|
2 Count of Participants
|
0 Count of Participants
|
|
Number of Participants With Notable Abnormalities in Vital Signs in the DDI Phase
DBP low (<=50mmHg with decrease from baseline of >=15mmHg)
|
0 Count of Participants
|
0 Count of Participants
|
1 Count of Participants
|
|
Number of Participants With Notable Abnormalities in Vital Signs in the DDI Phase
PR low (<=50bpm with decrease from baseline of >=15bpm）
|
0 Count of Participants
|
0 Count of Participants
|
1 Count of Participants
|
|
Number of Participants With Notable Abnormalities in Vital Signs in the DDI Phase
Temperature low
|
2 Count of Participants
|
3 Count of Participants
|
1 Count of Participants
|
SECONDARY outcome
Timeframe: After 1st dose of encorafenib/binimetinib on Day 1 and up to Day 28 visit in the DDI PhasePopulation: All participants who received at least 1 dose of encorafenib/binimetinib. Here, 'Number Analyzed' signifies participants evaluable for the specified rows.
Triplicate 12-lead ECG were performed after the participant had rested quietly for at least 10 minutes in a supine position. ECG parameters included RR interval, PR interval, QRS complex, QT interval, corrected QT (QTc) interval, Bazett's correction QT (QTcB) interval, Heart Rate and Fridericia's correction (QTcF) interval. The criterion included: QTcF \>450 - \<=480 mesc, \>480 - \<=500 msec, \>500 msec, increase from baseline \>30 - \<=60 msec and increase from baseline \>60 msec. QT interval \>450 - \<=480 msec, \>480 - \<=500 msec, \>500 msec, increase from baseline \>30 - \<=60 msec and increase from baseline \>60 msec. Heart rate increase from baseline \>25% and value \>100 bpm and decrease from baseline \>25% and value \<60 bpm. PR interval increase from baseline \>25% and value \>200 msec. QRS interval increase from baseline \>25% and value \>110 msec. Any new post-baseline notable ECG findings in the DDI phase was collected and reported in this outcome measure.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=27 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
n=12 Participants
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
n=15 Participants
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Number of Participants With Notable Electrocardiogram (ECG) Findings in the DDI Phase
New QTcF >500 msec
|
0 Count of Participants
|
1 Count of Participants
|
0 Count of Participants
|
|
Number of Participants With Notable Electrocardiogram (ECG) Findings in the DDI Phase
New QTcF Increase from baseline >30 - <=60 msec
|
5 Count of Participants
|
3 Count of Participants
|
2 Count of Participants
|
|
Number of Participants With Notable Electrocardiogram (ECG) Findings in the DDI Phase
New Heart rate Decrease from baseline >25% and value <60 bpm
|
0 Count of Participants
|
0 Count of Participants
|
0 Count of Participants
|
|
Number of Participants With Notable Electrocardiogram (ECG) Findings in the DDI Phase
New QT >480 - <=500 msec
|
1 Count of Participants
|
1 Count of Participants
|
1 Count of Participants
|
|
Number of Participants With Notable Electrocardiogram (ECG) Findings in the DDI Phase
New QT >500 msec
|
0 Count of Participants
|
0 Count of Participants
|
0 Count of Participants
|
|
Number of Participants With Notable Electrocardiogram (ECG) Findings in the DDI Phase
New QT Increase from baseline >30 - <=60 msec
|
13 Count of Participants
|
5 Count of Participants
|
9 Count of Participants
|
|
Number of Participants With Notable Electrocardiogram (ECG) Findings in the DDI Phase
New QT Increase from baseline >60 msec
|
2 Count of Participants
|
0 Count of Participants
|
1 Count of Participants
|
|
Number of Participants With Notable Electrocardiogram (ECG) Findings in the DDI Phase
New Heart rate Increase from baseline >25% and value >100 bpm
|
0 Count of Participants
|
0 Count of Participants
|
0 Count of Participants
|
|
Number of Participants With Notable Electrocardiogram (ECG) Findings in the DDI Phase
New PR Increase from baseline >25% and value >200 msec
|
2 Count of Participants
|
1 Count of Participants
|
3 Count of Participants
|
|
Number of Participants With Notable Electrocardiogram (ECG) Findings in the DDI Phase
New QRS Increase from baseline >25% and value >110 msec
|
0 Count of Participants
|
1 Count of Participants
|
0 Count of Participants
|
|
Number of Participants With Notable Electrocardiogram (ECG) Findings in the DDI Phase
New QTcF >450 - <=480 mesc
|
6 Count of Participants
|
3 Count of Participants
|
2 Count of Participants
|
|
Number of Participants With Notable Electrocardiogram (ECG) Findings in the DDI Phase
New QTcF >480 - <=500 msec
|
1 Count of Participants
|
0 Count of Participants
|
1 Count of Participants
|
|
Number of Participants With Notable Electrocardiogram (ECG) Findings in the DDI Phase
New QTcF Increase from baseline >60 msec
|
0 Count of Participants
|
0 Count of Participants
|
0 Count of Participants
|
|
Number of Participants With Notable Electrocardiogram (ECG) Findings in the DDI Phase
New QT >450 - <=480 msec
|
6 Count of Participants
|
0 Count of Participants
|
4 Count of Participants
|
SECONDARY outcome
Timeframe: After 1st dose of encorafenib/binimetinib on Day 1 and up to Day 28 visit in the DDI PhasePopulation: All participants who received at least 1 dose of encorafenib/binimetinib.
LVEF abnormalities are defined according to CTCAE grade version 4.03. Participants was considered as having a LVEF abnormality if the worst post-baseline value was Grade 2, 3, or 4 according to the following classification: Grade 0: Non-missing value below Grade 2; Grade 2: LVEF between 40% and 50% or absolute change from baseline between -10% and \<-20%; Grade 3: LVEF between 20% and 39% or absolute change from baseline lower than or equal to -20%; Grade 4: LVEF lower than 20%.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=27 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
n=12 Participants
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
n=15 Participants
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Number of Participants With Left Ventricular Ejection Fraction (LVEF) Abnormalities in the DDI Phase
|
4 Count of Participants
|
2 Count of Participants
|
0 Count of Participants
|
SECONDARY outcome
Timeframe: After 1st dose of encorafenib/binimetinib on Day 1 up to 30 days after the post-DDI PhasePopulation: All participants who received at least 1 dose of encorafenib/binimetinib.
An AE was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were those with initial onset or increasing in severity between the first dose of encorafenib/binimetinib and up to 30 days after treatment discontinuation. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. SAEs were adjudicated according to the investigator's assessment. Treatment-related AEs and SAEs were determined by the investigator. Any significant findings in the laboratory test, physical examinations, ophthalmic examinations, vital signs, ECG tests were captured as an AE.
Outcome measures
| Measure |
Arm 1 - CYP Probe Cocktail
n=25 Participants
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion
n=12 Participants
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
n=15 Participants
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Post-DDI Phase
AEs requiring additional therapy (treatment-related)
|
7 Count of Participants
|
2 Count of Participants
|
0 Count of Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Post-DDI Phase
Deaths
|
1 Count of Participants
|
1 Count of Participants
|
3 Count of Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Post-DDI Phase
Participants with all-causality TEAEs
|
17 Count of Participants
|
5 Count of Participants
|
4 Count of Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Post-DDI Phase
Participants with treatment-related TEAEs
|
10 Count of Participants
|
2 Count of Participants
|
2 Count of Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Post-DDI Phase
Participants with all-causality SAEs
|
11 Count of Participants
|
3 Count of Participants
|
4 Count of Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Post-DDI Phase
Participants with treatment-related SAEs
|
4 Count of Participants
|
0 Count of Participants
|
1 Count of Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Post-DDI Phase
AEs leading to study drug discontinuation (all-causality)
|
4 Count of Participants
|
1 Count of Participants
|
2 Count of Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Post-DDI Phase
AEs leading to study drug discontinuation (treatment-related)
|
2 Count of Participants
|
0 Count of Participants
|
1 Count of Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Post-DDI Phase
AEs requiring dose interruption (all-causality)
|
10 Count of Participants
|
3 Count of Participants
|
1 Count of Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Post-DDI Phase
AEs requiring dose interruption (treatment-related)
|
7 Count of Participants
|
2 Count of Participants
|
1 Count of Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Post-DDI Phase
AEs requiring dose reduction (all-causality)
|
1 Count of Participants
|
0 Count of Participants
|
0 Count of Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Post-DDI Phase
AEs requiring dose reduction (treatment-related)
|
1 Count of Participants
|
0 Count of Participants
|
0 Count of Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Post-DDI Phase
AEs requiring additional therapy (all-causality)
|
14 Count of Participants
|
4 Count of Participants
|
2 Count of Participants
|
Adverse Events
Arm 1 - CYP Probe Cocktail (DDI Phase)
Serious events: 2 serious events
Other events: 25 other events
Deaths: 0 deaths
Arm 2 - Rosuvastatin and Bupropion (DDI Phase)
Serious events: 1 serious events
Other events: 9 other events
Deaths: 0 deaths
Arm 3 - Modafinil (DDI Phase)
Serious events: 0 serious events
Other events: 11 other events
Deaths: 0 deaths
Arm 1 - CYP Probe Cocktail （Post-DDI Phase)
Serious events: 11 serious events
Other events: 4 other events
Deaths: 1 deaths
Arm 2 - Rosuvastatin and Bupropion (Post-DDI Phase)
Serious events: 3 serious events
Other events: 4 other events
Deaths: 2 deaths
Arm 3 - Modafinil (Post-DDI Phase)
Serious events: 4 serious events
Other events: 3 other events
Deaths: 3 deaths
Serious adverse events
| Measure |
Arm 1 - CYP Probe Cocktail (DDI Phase)
n=27 participants at risk
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion (DDI Phase)
n=12 participants at risk
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
n=15 participants at risk
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
Arm 1 - CYP Probe Cocktail （Post-DDI Phase)
n=25 participants at risk
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion (Post-DDI Phase)
n=12 participants at risk
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (Post-DDI Phase)
n=15 participants at risk
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|---|---|---|
|
Hepatobiliary disorders
Hypertransaminasaemia
|
0.00%
0/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
4.0%
1/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Gastrointestinal disorders
Large intestine perforation
|
0.00%
0/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
4.0%
1/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Nervous system disorders
Seizure
|
0.00%
0/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
6.7%
1/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to central nervous system
|
0.00%
0/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
6.7%
1/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Infections and infestations
Cellulitis
|
0.00%
0/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
6.7%
1/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
6.7%
1/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm progression
|
0.00%
0/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
8.3%
1/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
13.3%
2/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
General disorders
Pyrexia
|
7.4%
2/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
8.3%
1/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
8.0%
2/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Infections and infestations
Escherichia sepsis
|
0.00%
0/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
8.3%
1/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
0.00%
0/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
16.7%
2/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
4.0%
1/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Gastrointestinal disorders
Abdominal distension
|
0.00%
0/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
4.0%
1/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
4.0%
1/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
0.00%
0/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
4.0%
1/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Gastrointestinal disorders
Vomiting
|
7.4%
2/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
8.0%
2/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Vascular disorders
Hypotension
|
0.00%
0/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
4.0%
1/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Injury, poisoning and procedural complications
Post procedural haemorrhage
|
0.00%
0/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
4.0%
1/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
4.0%
1/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
General disorders
Influenza like illness
|
0.00%
0/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
4.0%
1/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Nervous system disorders
Syncope
|
0.00%
0/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
4.0%
1/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Nervous system disorders
Haemorrhage intracranial
|
0.00%
0/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
4.0%
1/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Gastrointestinal disorders
Nausea
|
3.7%
1/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
General disorders
Chills
|
3.7%
1/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Infections and infestations
Pyelonephritis
|
0.00%
0/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
4.0%
1/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Infections and infestations
Escherichia bacteraemia
|
0.00%
0/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
4.0%
1/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Infections and infestations
Septic shock
|
0.00%
0/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
4.0%
1/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
4.0%
1/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Injury, poisoning and procedural complications
Head injury
|
0.00%
0/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
4.0%
1/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Gastrointestinal disorders
Colitis
|
0.00%
0/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
4.0%
1/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Infections and infestations
Clostridium difficile colitis
|
0.00%
0/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
4.0%
1/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
Other adverse events
| Measure |
Arm 1 - CYP Probe Cocktail (DDI Phase)
n=27 participants at risk
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion (DDI Phase)
n=12 participants at risk
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (DDI Phase)
n=15 participants at risk
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
Arm 1 - CYP Probe Cocktail （Post-DDI Phase)
n=25 participants at risk
Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 2 - Rosuvastatin and Bupropion (Post-DDI Phase)
n=12 participants at risk
Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).
|
Arm 3 - Modafinil (Post-DDI Phase)
n=15 participants at risk
Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).
|
|---|---|---|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
33.3%
4/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
6.7%
1/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
8.3%
1/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
6.7%
1/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Blood and lymphatic system disorders
Iron deficiency anaemia
|
0.00%
0/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
8.3%
1/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Eye disorders
Retinal detachment
|
0.00%
0/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
16.7%
2/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Eye disorders
Periorbital discomfort
|
0.00%
0/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
8.3%
1/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Eye disorders
Photophobia
|
0.00%
0/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
8.3%
1/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Eye disorders
Punctate keratitis
|
0.00%
0/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
8.3%
1/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Eye disorders
Serous retinal detachment
|
0.00%
0/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
8.3%
1/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Eye disorders
Visual impairment
|
0.00%
0/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
8.3%
1/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Gastrointestinal disorders
Nausea
|
33.3%
9/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
41.7%
5/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
26.7%
4/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Gastrointestinal disorders
Diarrhoea
|
29.6%
8/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
25.0%
3/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
26.7%
4/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
8.3%
1/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Gastrointestinal disorders
Vomiting
|
18.5%
5/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
16.7%
2/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
6.7%
1/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Gastrointestinal disorders
Abdominal pain
|
7.4%
2/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
8.3%
1/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
6.7%
1/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Gastrointestinal disorders
Constipation
|
18.5%
5/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
8.3%
1/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Gastrointestinal disorders
Malabsorption
|
0.00%
0/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
8.3%
1/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
0.00%
0/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
8.3%
1/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
6.7%
1/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
General disorders
Fatigue
|
18.5%
5/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
25.0%
3/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
13.3%
2/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
General disorders
Pyrexia
|
11.1%
3/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
16.7%
2/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
General disorders
Asthenia
|
0.00%
0/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
8.3%
1/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
20.0%
3/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
8.3%
1/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
General disorders
Catheter site pain
|
0.00%
0/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
8.3%
1/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
General disorders
Malaise
|
0.00%
0/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
8.3%
1/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Investigations
Blood creatine phosphokinase increased
|
11.1%
3/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
8.3%
1/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
6.7%
1/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Investigations
Blood lactate dehydrogenase increased
|
0.00%
0/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
8.3%
1/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Investigations
Ejection fraction decreased
|
0.00%
0/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
8.3%
1/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
11.1%
3/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
16.7%
2/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
13.3%
2/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
8.3%
1/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
0.00%
0/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
8.3%
1/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Metabolism and nutrition disorders
Hypoproteinaemia
|
0.00%
0/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
8.3%
1/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Metabolism and nutrition disorders
Iron deficiency
|
0.00%
0/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
8.3%
1/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
7.4%
2/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
16.7%
2/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
6.7%
1/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
8.3%
1/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
0.00%
0/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
8.3%
1/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
6.7%
1/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Nervous system disorders
Headache
|
11.1%
3/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
16.7%
2/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
20.0%
3/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Nervous system disorders
Dizziness
|
14.8%
4/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
8.3%
1/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
6.7%
1/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Renal and urinary disorders
Dysuria
|
0.00%
0/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
8.3%
1/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
8.3%
1/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
7.4%
2/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
8.3%
1/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome
|
0.00%
0/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
16.7%
2/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
11.1%
3/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
6.7%
1/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
8.3%
1/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Blood and lymphatic system disorders
Lymphocytosis
|
0.00%
0/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
6.7%
1/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
6.7%
1/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Eye disorders
Vision blurred
|
22.2%
6/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
13.3%
2/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Ear and labyrinth disorders
Ear pain
|
0.00%
0/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
6.7%
1/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Eye disorders
Optic disc drusen
|
0.00%
0/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
6.7%
1/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Eye disorders
Subretinal fluid
|
0.00%
0/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
6.7%
1/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
7.4%
2/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
6.7%
1/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Gastrointestinal disorders
Dry mouth
|
0.00%
0/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
6.7%
1/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
General disorders
Inflammation
|
0.00%
0/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
6.7%
1/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Infections and infestations
Oral candidiasis
|
0.00%
0/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
6.7%
1/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Investigations
Alanine aminotransferase increased
|
7.4%
2/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
6.7%
1/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
6.7%
1/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Investigations
Blood creatinine increased
|
11.1%
3/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
6.7%
1/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Investigations
Weight decreased
|
0.00%
0/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
6.7%
1/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Musculoskeletal and connective tissue disorders
Coccydynia
|
0.00%
0/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
6.7%
1/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
6.7%
1/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain
|
0.00%
0/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
6.7%
1/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
6.7%
1/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
6.7%
1/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Psychiatric disorders
Restlessness
|
0.00%
0/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
6.7%
1/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
0.00%
0/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
6.7%
1/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Skin and subcutaneous tissue disorders
Skin haemorrhage
|
0.00%
0/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
6.7%
1/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Gastrointestinal disorders
Abdominal distension
|
11.1%
3/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Investigations
Lipase increased
|
22.2%
6/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
8.0%
2/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Investigations
Amylase increased
|
11.1%
3/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Investigations
Blood alkaline phosphatase increased
|
7.4%
2/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Investigations
Electrocardiogram QT prolonged
|
7.4%
2/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Skin and subcutaneous tissue disorders
Rash
|
7.4%
2/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Vascular disorders
Hypotension
|
7.4%
2/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
8.3%
1/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.00%
0/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
8.0%
2/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to central nervous system
|
0.00%
0/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
6.7%
1/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
|
Vascular disorders
Hypertension
|
7.4%
2/27 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/25 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/12 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
0.00%
0/15 • DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3
An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60