Trial Outcomes & Findings for A Study of Effect of Multiple Doses of LOXO-305 on the Pharmacokinetics of Single Oral Doses of CYP1A2, CYP2C9, CYP2C19 Substrates in Healthy Participants (NCT NCT06215430)
NCT ID: NCT06215430
Last Updated: 2025-03-10
Results Overview
t1/2 of warfarin was reported.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
16 participants
Primary outcome timeframe
Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose)
Results posted on
2025-03-10
Participant Flow
Participant milestones
| Measure |
Period 1: Probe Drug Cocktail
Participants received 200 milligrams (mg) caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet on Day 1.
|
Period 2: Pirtobrutinib + Probe Drug Cocktail
Participants received oral dose of 200 mg Pirtobrutinib once daily (QD) from Day 6 to Day 19. On Day 15, Pirtobrutinib was co-administered with 200 mg caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet.
There was a 5-day washout period between the probe drug cocktail on Day 1 (Period 1) and the first dose of Pirtobrutinib on Day 6 (Period 2).
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|---|---|---|
|
Period 1 (Days 1 - 5)
STARTED
|
16
|
0
|
|
Period 1 (Days 1 - 5)
Received at Least 1 Dose of Study Drug
|
16
|
0
|
|
Period 1 (Days 1 - 5)
COMPLETED
|
16
|
0
|
|
Period 1 (Days 1 - 5)
NOT COMPLETED
|
0
|
0
|
|
Period 2 (Days 6 - 23)
STARTED
|
0
|
16
|
|
Period 2 (Days 6 - 23)
Received at Least 1 Dose of Study Drug
|
0
|
16
|
|
Period 2 (Days 6 - 23)
COMPLETED
|
0
|
16
|
|
Period 2 (Days 6 - 23)
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Study of Effect of Multiple Doses of LOXO-305 on the Pharmacokinetics of Single Oral Doses of CYP1A2, CYP2C9, CYP2C19 Substrates in Healthy Participants
Baseline characteristics by cohort
| Measure |
Overall Study Participants
n=16 Participants
* Period 1: Participants received 200 milligrams (mg) caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet on Day 1.
* Period 2: Participants received oral dose of 200 mg Pirtobrutinib once daily (QD) from Day 6 to Day 19. On Day 15, Pirtobrutinib was co-administered with 200 mg caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet.
* There was a 5-day washout period between the probe drug cocktail on Day 1 (Period 1) and the first dose of Pirtobrutinib on Day 6 (Period 2).
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|---|---|
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Age, Continuous
|
39.1 years
STANDARD_DEVIATION 9.46 • n=99 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
12 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
4 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
12 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Black or African American
|
7 Participants
n=99 Participants
|
|
Race (NIH/OMB)
White
|
9 Participants
n=99 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
|
Region of Enrollment
United States
|
16 participants
n=99 Participants
|
PRIMARY outcome
Timeframe: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose)Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
Area under the concentration time curve (AUC) from hour 0 to 24 hours post-dose (AUC0-24) of caffeine was reported.
Outcome measures
| Measure |
Period 1: Probe Drug Cocktail
n=16 Participants
In period 1, Participants received 200 milligrams (mg) caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet on Day 1.
|
Period 2: Pirtobrutinib + Probe Drug Cocktail
n=16 Participants
In Period 2, Participants received oral dose of 200 mg Pirtobrutinib once daily (QD) from Day 6 to Day 19. On Day 15, Pirtobrutinib was co-administered with 200 mg caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet.
|
|---|---|---|
|
Area Under the Concentration Time Curve (AUC) From Hour 0 to 24 Hours Post-Dose (AUC0-24): Caffeine
|
39100 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 31.8
|
37400 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 31.8
|
PRIMARY outcome
Timeframe: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose)Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed. Here 'overall number of participants analyzed' signifies participants with available data for this outcome measure.
AUC0-24 of Paraxanthine was reported.
Outcome measures
| Measure |
Period 1: Probe Drug Cocktail
n=16 Participants
In period 1, Participants received 200 milligrams (mg) caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet on Day 1.
|
Period 2: Pirtobrutinib + Probe Drug Cocktail
n=4 Participants
In Period 2, Participants received oral dose of 200 mg Pirtobrutinib once daily (QD) from Day 6 to Day 19. On Day 15, Pirtobrutinib was co-administered with 200 mg caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet.
|
|---|---|---|
|
Area Under the Concentration Time Curve (AUC) From Hour 0 to 24 Hours Post-Dose (AUC0-24): Paraxanthine
|
20600 h*ng/mL
Geometric Coefficient of Variation 12.1
|
18600 h*ng/mL
Geometric Coefficient of Variation 17.7
|
PRIMARY outcome
Timeframe: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose)Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
AUC0-24 of Omeprazole was reported.
Outcome measures
| Measure |
Period 1: Probe Drug Cocktail
n=16 Participants
In period 1, Participants received 200 milligrams (mg) caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet on Day 1.
|
Period 2: Pirtobrutinib + Probe Drug Cocktail
n=16 Participants
In Period 2, Participants received oral dose of 200 mg Pirtobrutinib once daily (QD) from Day 6 to Day 19. On Day 15, Pirtobrutinib was co-administered with 200 mg caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet.
|
|---|---|---|
|
Area Under the Concentration Time Curve (AUC) From Hour 0 to 24 Hours Post-Dose (AUC0-24): Omeprazole
|
2000 h*ng/mL
Geometric Coefficient of Variation 100.9
|
3120 h*ng/mL
Geometric Coefficient of Variation 61.6
|
PRIMARY outcome
Timeframe: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose)Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
AUC(0-24) of Warfarin was reported.
Outcome measures
| Measure |
Period 1: Probe Drug Cocktail
n=16 Participants
In period 1, Participants received 200 milligrams (mg) caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet on Day 1.
|
Period 2: Pirtobrutinib + Probe Drug Cocktail
n=16 Participants
In Period 2, Participants received oral dose of 200 mg Pirtobrutinib once daily (QD) from Day 6 to Day 19. On Day 15, Pirtobrutinib was co-administered with 200 mg caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet.
|
|---|---|---|
|
Area Under the Concentration Time Curve (AUC) From Hour 0 to 24 Hours Post-Dose (AUC0-24): Warfarin
|
7320 h*ng/mL
Geometric Coefficient of Variation 19.7
|
7880 h*ng/mL
Geometric Coefficient of Variation 18.3
|
PRIMARY outcome
Timeframe: Period 2, Day 15 (0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours Post dose)Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
AUC0-24 of Pirtobrutinib was reported.
Outcome measures
| Measure |
Period 1: Probe Drug Cocktail
n=16 Participants
In period 1, Participants received 200 milligrams (mg) caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet on Day 1.
|
Period 2: Pirtobrutinib + Probe Drug Cocktail
In Period 2, Participants received oral dose of 200 mg Pirtobrutinib once daily (QD) from Day 6 to Day 19. On Day 15, Pirtobrutinib was co-administered with 200 mg caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet.
|
|---|---|---|
|
Area Under the Concentration Time Curve (AUC) From Hour 0 to 24 Hours Post-Dose (AUC0-24): Pirtobrutinib
|
119000 h*ng/mL
Geometric Coefficient of Variation 24.4
|
—
|
PRIMARY outcome
Timeframe: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose)Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
AUC from hour 0 to the last measurable concentration (AUC0-t) of caffeine was reported.
Outcome measures
| Measure |
Period 1: Probe Drug Cocktail
n=16 Participants
In period 1, Participants received 200 milligrams (mg) caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet on Day 1.
|
Period 2: Pirtobrutinib + Probe Drug Cocktail
n=16 Participants
In Period 2, Participants received oral dose of 200 mg Pirtobrutinib once daily (QD) from Day 6 to Day 19. On Day 15, Pirtobrutinib was co-administered with 200 mg caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet.
|
|---|---|---|
|
Area Under the Concentration-time Curve (AUC), From Hour 0 to the Last Measurable Concentration (AUC0-t): Caffeine
|
39100 h*ng/mL
Geometric Coefficient of Variation 31.8
|
37400 h*ng/mL
Geometric Coefficient of Variation 31.7
|
PRIMARY outcome
Timeframe: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose)Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
AUC0-t of Paraxanthine was reported.
Outcome measures
| Measure |
Period 1: Probe Drug Cocktail
n=16 Participants
In period 1, Participants received 200 milligrams (mg) caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet on Day 1.
|
Period 2: Pirtobrutinib + Probe Drug Cocktail
n=16 Participants
In Period 2, Participants received oral dose of 200 mg Pirtobrutinib once daily (QD) from Day 6 to Day 19. On Day 15, Pirtobrutinib was co-administered with 200 mg caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet.
|
|---|---|---|
|
Area Under the Concentration-time Curve (AUC), From Hour 0 to the Last Measurable Concentration (AUC0-t): Paraxanthine
|
20600 h*ng/mL
Geometric Coefficient of Variation 12.1
|
19400 h*ng/mL
Geometric Coefficient of Variation 14.0
|
PRIMARY outcome
Timeframe: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose)Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
AUC0-t of Omeprazole was reported.
Outcome measures
| Measure |
Period 1: Probe Drug Cocktail
n=16 Participants
In period 1, Participants received 200 milligrams (mg) caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet on Day 1.
|
Period 2: Pirtobrutinib + Probe Drug Cocktail
n=16 Participants
In Period 2, Participants received oral dose of 200 mg Pirtobrutinib once daily (QD) from Day 6 to Day 19. On Day 15, Pirtobrutinib was co-administered with 200 mg caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet.
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|---|---|---|
|
Area Under the Concentration Time Curve (AUC) From Hour 0 to the Last Measurable Concentration (AUC0-t): Omeprazole
|
1990 h*ng/mL
Geometric Coefficient of Variation 101.0
|
3110 h*ng/mL
Geometric Coefficient of Variation 61.7
|
PRIMARY outcome
Timeframe: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose)Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
AUC0-t of Warfarin was reported.
Outcome measures
| Measure |
Period 1: Probe Drug Cocktail
n=16 Participants
In period 1, Participants received 200 milligrams (mg) caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet on Day 1.
|
Period 2: Pirtobrutinib + Probe Drug Cocktail
n=16 Participants
In Period 2, Participants received oral dose of 200 mg Pirtobrutinib once daily (QD) from Day 6 to Day 19. On Day 15, Pirtobrutinib was co-administered with 200 mg caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet.
|
|---|---|---|
|
Area Under the Concentration Time Curve (AUC) From Hour 0 to the Last Measurable Concentration (AUC0-t): Warfarin
|
17300 h*ng/mL
Geometric Coefficient of Variation 19.1
|
19200 h*ng/mL
Geometric Coefficient of Variation 20.0
|
PRIMARY outcome
Timeframe: Period 2, Day 15 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, and 192 hours postdose)Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
AUC0-t of Pirtobrutinib was reported.
Outcome measures
| Measure |
Period 1: Probe Drug Cocktail
n=16 Participants
In period 1, Participants received 200 milligrams (mg) caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet on Day 1.
|
Period 2: Pirtobrutinib + Probe Drug Cocktail
In Period 2, Participants received oral dose of 200 mg Pirtobrutinib once daily (QD) from Day 6 to Day 19. On Day 15, Pirtobrutinib was co-administered with 200 mg caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet.
|
|---|---|---|
|
Area Under the Concentration Time Curve (AUC) From Hour 0 to the Last Measurable Concentration (AUC0-t): Pirtobrutinib
|
119000 h*ng/mL
Geometric Coefficient of Variation 24.4
|
—
|
PRIMARY outcome
Timeframe: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose)Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
AUC from hour 0 extrapolated to infinity (AUC0-inf) of Caffeine was reported.
Outcome measures
| Measure |
Period 1: Probe Drug Cocktail
n=16 Participants
In period 1, Participants received 200 milligrams (mg) caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet on Day 1.
|
Period 2: Pirtobrutinib + Probe Drug Cocktail
n=16 Participants
In Period 2, Participants received oral dose of 200 mg Pirtobrutinib once daily (QD) from Day 6 to Day 19. On Day 15, Pirtobrutinib was co-administered with 200 mg caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet.
|
|---|---|---|
|
Area Under the Concentration Time Curve (AUC) From Hour 0 Extrapolated to Infinity (AUC0-inf): Caffeine
|
42600 h*ng/mL
Geometric Coefficient of Variation 39.7
|
40000 h*ng/mL
Geometric Coefficient of Variation 37.5
|
PRIMARY outcome
Timeframe: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose)Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed. Here 'overall number of participants analyzed' signifies participants with available data for this outcome measure.
AUC0-inf of Paraxanthine was reported.
Outcome measures
| Measure |
Period 1: Probe Drug Cocktail
n=4 Participants
In period 1, Participants received 200 milligrams (mg) caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet on Day 1.
|
Period 2: Pirtobrutinib + Probe Drug Cocktail
n=4 Participants
In Period 2, Participants received oral dose of 200 mg Pirtobrutinib once daily (QD) from Day 6 to Day 19. On Day 15, Pirtobrutinib was co-administered with 200 mg caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet.
|
|---|---|---|
|
Area Under the Concentration Time Curve (AUC) From Hour 0 Extrapolated to Infinity (AUC0-inf): Paraxanthine
|
23100 h*ng/mL
Geometric Coefficient of Variation 10.1
|
20300 h*ng/mL
Geometric Coefficient of Variation 17.4
|
PRIMARY outcome
Timeframe: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose)Population: All participants who received a dose of study drug had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
AUC0-inf of omeprazole was reported.
Outcome measures
| Measure |
Period 1: Probe Drug Cocktail
n=16 Participants
In period 1, Participants received 200 milligrams (mg) caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet on Day 1.
|
Period 2: Pirtobrutinib + Probe Drug Cocktail
n=16 Participants
In Period 2, Participants received oral dose of 200 mg Pirtobrutinib once daily (QD) from Day 6 to Day 19. On Day 15, Pirtobrutinib was co-administered with 200 mg caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet.
|
|---|---|---|
|
Area Under the Concentration Time Curve (AUC) From Hour 0 Extrapolated to Infinity (AUC0-inf): Omeprazole
|
2000 h*ng/mL
Geometric Coefficient of Variation 101.0
|
3120 h*ng/mL
Geometric Coefficient of Variation 61.6
|
PRIMARY outcome
Timeframe: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose)Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
AUC0-inf of Warfarin was reported.
Outcome measures
| Measure |
Period 1: Probe Drug Cocktail
n=16 Participants
In period 1, Participants received 200 milligrams (mg) caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet on Day 1.
|
Period 2: Pirtobrutinib + Probe Drug Cocktail
n=16 Participants
In Period 2, Participants received oral dose of 200 mg Pirtobrutinib once daily (QD) from Day 6 to Day 19. On Day 15, Pirtobrutinib was co-administered with 200 mg caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet.
|
|---|---|---|
|
Area Under the Concentration Time Curve (AUC) From Hour 0 Extrapolated to Infinity (AUC0-inf): Warfarin
|
20100 h*ng/mL
Geometric Coefficient of Variation 21.1
|
22400 h*ng/mL
Geometric Coefficient of Variation 21.9
|
PRIMARY outcome
Timeframe: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose)Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
AUC0-inf (%AUCextrap) of caffeine was reported.
Outcome measures
| Measure |
Period 1: Probe Drug Cocktail
n=16 Participants
In period 1, Participants received 200 milligrams (mg) caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet on Day 1.
|
Period 2: Pirtobrutinib + Probe Drug Cocktail
n=16 Participants
In Period 2, Participants received oral dose of 200 mg Pirtobrutinib once daily (QD) from Day 6 to Day 19. On Day 15, Pirtobrutinib was co-administered with 200 mg caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet.
|
|---|---|---|
|
Percentage Extrapolation for AUC0-inf (%AUCextrap): Caffeine
|
5.20 percentage of AUCextrap
Geometric Coefficient of Variation 130.6
|
4.17 percentage of AUCextrap
Geometric Coefficient of Variation 149.3
|
PRIMARY outcome
Timeframe: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose)Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed. Here 'overall number of participants analyzed' signifies participants with available data for this outcome measure.
AUC0-inf (%AUCextrap) of Paraxanthine was reported.
Outcome measures
| Measure |
Period 1: Probe Drug Cocktail
n=4 Participants
In period 1, Participants received 200 milligrams (mg) caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet on Day 1.
|
Period 2: Pirtobrutinib + Probe Drug Cocktail
n=4 Participants
In Period 2, Participants received oral dose of 200 mg Pirtobrutinib once daily (QD) from Day 6 to Day 19. On Day 15, Pirtobrutinib was co-administered with 200 mg caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet.
|
|---|---|---|
|
Percentage Extrapolation for AUC0-inf (%AUCextrap): Paraxanthine
|
12.0 percentage of AUCextrap
Geometric Coefficient of Variation 58.3
|
7.45 percentage of AUCextrap
Geometric Coefficient of Variation 63.6
|
PRIMARY outcome
Timeframe: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose)Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
%AUCextrap of omeprazole was reported.
Outcome measures
| Measure |
Period 1: Probe Drug Cocktail
n=16 Participants
In period 1, Participants received 200 milligrams (mg) caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet on Day 1.
|
Period 2: Pirtobrutinib + Probe Drug Cocktail
n=16 Participants
In Period 2, Participants received oral dose of 200 mg Pirtobrutinib once daily (QD) from Day 6 to Day 19. On Day 15, Pirtobrutinib was co-administered with 200 mg caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet.
|
|---|---|---|
|
Percentage Extrapolation for AUC0-inf (%AUCextrap): Omeprazole
|
0.421 percentage of AUCextrap
Geometric Coefficient of Variation 84.3
|
0.302 percentage of AUCextrap
Geometric Coefficient of Variation 97.8
|
PRIMARY outcome
Timeframe: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose)Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
%AUCextrap of Warfarin was reported.
Outcome measures
| Measure |
Period 1: Probe Drug Cocktail
n=16 Participants
In period 1, Participants received 200 milligrams (mg) caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet on Day 1.
|
Period 2: Pirtobrutinib + Probe Drug Cocktail
n=16 Participants
In Period 2, Participants received oral dose of 200 mg Pirtobrutinib once daily (QD) from Day 6 to Day 19. On Day 15, Pirtobrutinib was co-administered with 200 mg caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet.
|
|---|---|---|
|
Percentage Extrapolation for AUC0-inf (%AUCextrap): Warfarin
|
13.1 percentage of AUCextrap
Geometric Coefficient of Variation 33.5
|
13.4 percentage of AUCextrap
Geometric Coefficient of Variation 32.7
|
PRIMARY outcome
Timeframe: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose)Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
CL/F for caffeine was reported.
Outcome measures
| Measure |
Period 1: Probe Drug Cocktail
n=16 Participants
In period 1, Participants received 200 milligrams (mg) caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet on Day 1.
|
Period 2: Pirtobrutinib + Probe Drug Cocktail
n=16 Participants
In Period 2, Participants received oral dose of 200 mg Pirtobrutinib once daily (QD) from Day 6 to Day 19. On Day 15, Pirtobrutinib was co-administered with 200 mg caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet.
|
|---|---|---|
|
Apparent Systemic Clearance (CL/F): Caffeine
|
4.70 Liter per hour (L/h)
Geometric Coefficient of Variation 39.7
|
5.00 Liter per hour (L/h)
Geometric Coefficient of Variation 37.5
|
PRIMARY outcome
Timeframe: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose)Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
CL/F of omeprazole was reported.
Outcome measures
| Measure |
Period 1: Probe Drug Cocktail
n=16 Participants
In period 1, Participants received 200 milligrams (mg) caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet on Day 1.
|
Period 2: Pirtobrutinib + Probe Drug Cocktail
n=16 Participants
In Period 2, Participants received oral dose of 200 mg Pirtobrutinib once daily (QD) from Day 6 to Day 19. On Day 15, Pirtobrutinib was co-administered with 200 mg caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet.
|
|---|---|---|
|
Apparent Systemic Clearance (CL/F): Omeprazole
|
20.0 L/h
Geometric Coefficient of Variation 101.0
|
12.8 L/h
Geometric Coefficient of Variation 61.6
|
PRIMARY outcome
Timeframe: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose)Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
CL/F of warfarin was reported.
Outcome measures
| Measure |
Period 1: Probe Drug Cocktail
n=16 Participants
In period 1, Participants received 200 milligrams (mg) caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet on Day 1.
|
Period 2: Pirtobrutinib + Probe Drug Cocktail
n=16 Participants
In Period 2, Participants received oral dose of 200 mg Pirtobrutinib once daily (QD) from Day 6 to Day 19. On Day 15, Pirtobrutinib was co-administered with 200 mg caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet.
|
|---|---|---|
|
Apparent Systemic Clearance (CL/F): Warfarin
|
0.497 L/h
Geometric Coefficient of Variation 21.1
|
0.447 L/h
Geometric Coefficient of Variation 21.9
|
PRIMARY outcome
Timeframe: Period 2, Day 15 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, and 192 hours postdose)Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
CL/F of Pirtobrutinib was reported.
Outcome measures
| Measure |
Period 1: Probe Drug Cocktail
n=16 Participants
In period 1, Participants received 200 milligrams (mg) caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet on Day 1.
|
Period 2: Pirtobrutinib + Probe Drug Cocktail
In Period 2, Participants received oral dose of 200 mg Pirtobrutinib once daily (QD) from Day 6 to Day 19. On Day 15, Pirtobrutinib was co-administered with 200 mg caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet.
|
|---|---|---|
|
Apparent Systemic Clearance (CL/F): Pirtobrutinib
|
1.68 L/h
Geometric Coefficient of Variation 24.4
|
—
|
PRIMARY outcome
Timeframe: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose)Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
Cmax of caffeine was reported.
Outcome measures
| Measure |
Period 1: Probe Drug Cocktail
n=16 Participants
In period 1, Participants received 200 milligrams (mg) caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet on Day 1.
|
Period 2: Pirtobrutinib + Probe Drug Cocktail
n=16 Participants
In Period 2, Participants received oral dose of 200 mg Pirtobrutinib once daily (QD) from Day 6 to Day 19. On Day 15, Pirtobrutinib was co-administered with 200 mg caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet.
|
|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax): Caffeine
|
5060 ng/mL
Geometric Coefficient of Variation 17.6
|
4990 ng/mL
Geometric Coefficient of Variation 14.5
|
PRIMARY outcome
Timeframe: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose)Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
Cmax of Paraxanthine was reported.
Outcome measures
| Measure |
Period 1: Probe Drug Cocktail
n=16 Participants
In period 1, Participants received 200 milligrams (mg) caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet on Day 1.
|
Period 2: Pirtobrutinib + Probe Drug Cocktail
n=16 Participants
In Period 2, Participants received oral dose of 200 mg Pirtobrutinib once daily (QD) from Day 6 to Day 19. On Day 15, Pirtobrutinib was co-administered with 200 mg caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet.
|
|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax): Paraxanthine
|
1200 ng/mL
Geometric Coefficient of Variation 14.3
|
1150 ng/mL
Geometric Coefficient of Variation 14.6
|
PRIMARY outcome
Timeframe: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose)Population: All participants who received a dose of study drug had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
Cmax of omeprazole was reported.
Outcome measures
| Measure |
Period 1: Probe Drug Cocktail
n=16 Participants
In period 1, Participants received 200 milligrams (mg) caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet on Day 1.
|
Period 2: Pirtobrutinib + Probe Drug Cocktail
n=16 Participants
In Period 2, Participants received oral dose of 200 mg Pirtobrutinib once daily (QD) from Day 6 to Day 19. On Day 15, Pirtobrutinib was co-administered with 200 mg caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet.
|
|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax): Omeprazole
|
901 ng/mL
Geometric Coefficient of Variation 58.0
|
1350 ng/mL
Geometric Coefficient of Variation 42.3
|
PRIMARY outcome
Timeframe: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose)Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
Cmax of warfarin was reported.
Outcome measures
| Measure |
Period 1: Probe Drug Cocktail
n=16 Participants
In period 1, Participants received 200 milligrams (mg) caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet on Day 1.
|
Period 2: Pirtobrutinib + Probe Drug Cocktail
n=16 Participants
In Period 2, Participants received oral dose of 200 mg Pirtobrutinib once daily (QD) from Day 6 to Day 19. On Day 15, Pirtobrutinib was co-administered with 200 mg caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet.
|
|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax): Warfarin
|
585 ng/mL
Geometric Coefficient of Variation 26.1
|
595 ng/mL
Geometric Coefficient of Variation 25.2
|
PRIMARY outcome
Timeframe: Period 2, Day 15 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, and 192 hours postdose)Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
Cmax of Pirtobrutinib was reported.
Outcome measures
| Measure |
Period 1: Probe Drug Cocktail
n=16 Participants
In period 1, Participants received 200 milligrams (mg) caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet on Day 1.
|
Period 2: Pirtobrutinib + Probe Drug Cocktail
In Period 2, Participants received oral dose of 200 mg Pirtobrutinib once daily (QD) from Day 6 to Day 19. On Day 15, Pirtobrutinib was co-administered with 200 mg caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet.
|
|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax): Pirtobrutinib
|
9430 ng/mL
Geometric Coefficient of Variation 24.6
|
—
|
PRIMARY outcome
Timeframe: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose)Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
Tmax of caffeine was reported.
Outcome measures
| Measure |
Period 1: Probe Drug Cocktail
n=16 Participants
In period 1, Participants received 200 milligrams (mg) caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet on Day 1.
|
Period 2: Pirtobrutinib + Probe Drug Cocktail
n=16 Participants
In Period 2, Participants received oral dose of 200 mg Pirtobrutinib once daily (QD) from Day 6 to Day 19. On Day 15, Pirtobrutinib was co-administered with 200 mg caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet.
|
|---|---|---|
|
Time to Maximum Observed Plasma Concentration (Tmax): Caffeine
|
0.500 hour (h)
Interval 0.5 to 1.0
|
0.750 hour (h)
Interval 0.5 to 1.0
|
PRIMARY outcome
Timeframe: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose)Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
Tmax of Paraxanthine was reported.
Outcome measures
| Measure |
Period 1: Probe Drug Cocktail
n=16 Participants
In period 1, Participants received 200 milligrams (mg) caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet on Day 1.
|
Period 2: Pirtobrutinib + Probe Drug Cocktail
n=16 Participants
In Period 2, Participants received oral dose of 200 mg Pirtobrutinib once daily (QD) from Day 6 to Day 19. On Day 15, Pirtobrutinib was co-administered with 200 mg caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet.
|
|---|---|---|
|
Time to Maximum Observed Plasma Concentration (Tmax): Paraxanthine
|
10.0 hour (h)
Interval 6.0 to 24.0
|
8.01 hour (h)
Interval 6.0 to 12.0
|
PRIMARY outcome
Timeframe: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose)Population: All participants who received a dose of study drug had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
Tmax of omeprazole was reported.
Outcome measures
| Measure |
Period 1: Probe Drug Cocktail
n=16 Participants
In period 1, Participants received 200 milligrams (mg) caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet on Day 1.
|
Period 2: Pirtobrutinib + Probe Drug Cocktail
n=16 Participants
In Period 2, Participants received oral dose of 200 mg Pirtobrutinib once daily (QD) from Day 6 to Day 19. On Day 15, Pirtobrutinib was co-administered with 200 mg caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet.
|
|---|---|---|
|
Time to Maximum Observed Plasma Concentration (Tmax): Omeprazole
|
2.00 hour (h)
Interval 1.5 to 4.0
|
2.50 hour (h)
Interval 1.5 to 4.0
|
PRIMARY outcome
Timeframe: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose)Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
Tmax of warfarin was reported.
Outcome measures
| Measure |
Period 1: Probe Drug Cocktail
n=16 Participants
In period 1, Participants received 200 milligrams (mg) caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet on Day 1.
|
Period 2: Pirtobrutinib + Probe Drug Cocktail
n=16 Participants
In Period 2, Participants received oral dose of 200 mg Pirtobrutinib once daily (QD) from Day 6 to Day 19. On Day 15, Pirtobrutinib was co-administered with 200 mg caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet.
|
|---|---|---|
|
Time to Maximum Observed Plasma Concentration (Tmax): Warfarin
|
1.50 hour (h)
Interval 0.5 to 3.0
|
1.50 hour (h)
Interval 0.25 to 3.0
|
PRIMARY outcome
Timeframe: Period 2, Day 15 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, and 192 hours postdose)Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
Tmax of Pirtobrutinib was reported.
Outcome measures
| Measure |
Period 1: Probe Drug Cocktail
n=16 Participants
In period 1, Participants received 200 milligrams (mg) caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet on Day 1.
|
Period 2: Pirtobrutinib + Probe Drug Cocktail
In Period 2, Participants received oral dose of 200 mg Pirtobrutinib once daily (QD) from Day 6 to Day 19. On Day 15, Pirtobrutinib was co-administered with 200 mg caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet.
|
|---|---|---|
|
Time to Maximum Observed Plasma Concentration (Tmax): Pirtobrutinib
|
2.50 hour (h)
Interval 0.767 to 4.0
|
—
|
PRIMARY outcome
Timeframe: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose)Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
λZ of caffeine was reported.
Outcome measures
| Measure |
Period 1: Probe Drug Cocktail
n=16 Participants
In period 1, Participants received 200 milligrams (mg) caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet on Day 1.
|
Period 2: Pirtobrutinib + Probe Drug Cocktail
n=16 Participants
In Period 2, Participants received oral dose of 200 mg Pirtobrutinib once daily (QD) from Day 6 to Day 19. On Day 15, Pirtobrutinib was co-administered with 200 mg caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet.
|
|---|---|---|
|
Apparent Terminal Elimination Rate Constant (λZ): Caffeine
|
0.116 1/hour (1/h)
Geometric Coefficient of Variation 37.8
|
0.127 1/hour (1/h)
Geometric Coefficient of Variation 34.6
|
PRIMARY outcome
Timeframe: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose)Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed. Here 'overall number of participants analyzed' signifies participants with available data for this outcome measure.
λZ of Paraxanthine was reported.
Outcome measures
| Measure |
Period 1: Probe Drug Cocktail
n=4 Participants
In period 1, Participants received 200 milligrams (mg) caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet on Day 1.
|
Period 2: Pirtobrutinib + Probe Drug Cocktail
n=4 Participants
In Period 2, Participants received oral dose of 200 mg Pirtobrutinib once daily (QD) from Day 6 to Day 19. On Day 15, Pirtobrutinib was co-administered with 200 mg caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet.
|
|---|---|---|
|
Apparent Terminal Elimination Rate Constant (λZ): Paraxanthine
|
0.0966 1/hour (1/h)
Geometric Coefficient of Variation 24.0
|
0.120 1/hour (1/h)
Geometric Coefficient of Variation 21.8
|
PRIMARY outcome
Timeframe: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose)Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
λZ of omeprazole was reported.
Outcome measures
| Measure |
Period 1: Probe Drug Cocktail
n=16 Participants
In period 1, Participants received 200 milligrams (mg) caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet on Day 1.
|
Period 2: Pirtobrutinib + Probe Drug Cocktail
n=16 Participants
In Period 2, Participants received oral dose of 200 mg Pirtobrutinib once daily (QD) from Day 6 to Day 19. On Day 15, Pirtobrutinib was co-administered with 200 mg caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet.
|
|---|---|---|
|
Apparent Terminal Elimination Rate Constant (λZ): Omeprazole
|
0.611 1/hour (1/h)
Geometric Coefficient of Variation 48.4
|
0.578 1/hour (1/h)
Geometric Coefficient of Variation 37.2
|
PRIMARY outcome
Timeframe: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose)Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
λZ of warfarin was reported.
Outcome measures
| Measure |
Period 1: Probe Drug Cocktail
n=16 Participants
In period 1, Participants received 200 milligrams (mg) caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet on Day 1.
|
Period 2: Pirtobrutinib + Probe Drug Cocktail
n=16 Participants
In Period 2, Participants received oral dose of 200 mg Pirtobrutinib once daily (QD) from Day 6 to Day 19. On Day 15, Pirtobrutinib was co-administered with 200 mg caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet.
|
|---|---|---|
|
Apparent Terminal Elimination Rate Constant (λZ): Warfarin
|
0.0160 1/hour (1/h)
Geometric Coefficient of Variation 17.1
|
0.0165 1/hour (1/h)
Geometric Coefficient of Variation 16.4
|
PRIMARY outcome
Timeframe: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose)Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
Vz/F of caffeine was reported.
Outcome measures
| Measure |
Period 1: Probe Drug Cocktail
n=16 Participants
In period 1, Participants received 200 milligrams (mg) caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet on Day 1.
|
Period 2: Pirtobrutinib + Probe Drug Cocktail
n=16 Participants
In Period 2, Participants received oral dose of 200 mg Pirtobrutinib once daily (QD) from Day 6 to Day 19. On Day 15, Pirtobrutinib was co-administered with 200 mg caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet.
|
|---|---|---|
|
Apparent Volume of Distribution at Terminal Phase (Vz/F): Caffeine
|
40.4 Litre (L)
Geometric Coefficient of Variation 16.8
|
39.4 Litre (L)
Geometric Coefficient of Variation 18.1
|
PRIMARY outcome
Timeframe: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose)Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
Vz/F of omeprazole was reported.
Outcome measures
| Measure |
Period 1: Probe Drug Cocktail
n=16 Participants
In period 1, Participants received 200 milligrams (mg) caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet on Day 1.
|
Period 2: Pirtobrutinib + Probe Drug Cocktail
n=16 Participants
In Period 2, Participants received oral dose of 200 mg Pirtobrutinib once daily (QD) from Day 6 to Day 19. On Day 15, Pirtobrutinib was co-administered with 200 mg caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet.
|
|---|---|---|
|
Apparent Volume of Distribution at Terminal Phase (Vz/F): Omeprazole
|
32.8 Litre (L)
Geometric Coefficient of Variation 45.7
|
22.2 Litre (L)
Geometric Coefficient of Variation 33.6
|
PRIMARY outcome
Timeframe: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose)Population: All participants who received a dose of study drug had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
Vz/F of Warfarin was reported.
Outcome measures
| Measure |
Period 1: Probe Drug Cocktail
n=16 Participants
In period 1, Participants received 200 milligrams (mg) caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet on Day 1.
|
Period 2: Pirtobrutinib + Probe Drug Cocktail
n=16 Participants
In Period 2, Participants received oral dose of 200 mg Pirtobrutinib once daily (QD) from Day 6 to Day 19. On Day 15, Pirtobrutinib was co-administered with 200 mg caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet.
|
|---|---|---|
|
Apparent Volume of Distribution at Terminal Phase (Vz/F): Warfarin
|
31.0 Litre (L)
Geometric Coefficient of Variation 18.4
|
27.1 Litre (L)
Geometric Coefficient of Variation 21.0
|
PRIMARY outcome
Timeframe: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose)Population: All participants who received a dose of study drug had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
AUC Ratio of paraxanthine (Metabolite) to caffeine (Parent drug) was reported.
Outcome measures
| Measure |
Period 1: Probe Drug Cocktail
n=16 Participants
In period 1, Participants received 200 milligrams (mg) caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet on Day 1.
|
Period 2: Pirtobrutinib + Probe Drug Cocktail
n=16 Participants
In Period 2, Participants received oral dose of 200 mg Pirtobrutinib once daily (QD) from Day 6 to Day 19. On Day 15, Pirtobrutinib was co-administered with 200 mg caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet.
|
|---|---|---|
|
Metabolite to Parent Drug AUC Ratio (MRAUC): AUC Ratio of Paraxanthine to Caffeine
|
0.528 Ratio
Geometric Coefficient of Variation 29.1
|
0.518 Ratio
Geometric Coefficient of Variation 27.8
|
PRIMARY outcome
Timeframe: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose)Population: All participants who received a dose of study drug had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
MRT of caffeine was reported.
Outcome measures
| Measure |
Period 1: Probe Drug Cocktail
n=16 Participants
In period 1, Participants received 200 milligrams (mg) caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet on Day 1.
|
Period 2: Pirtobrutinib + Probe Drug Cocktail
n=16 Participants
In Period 2, Participants received oral dose of 200 mg Pirtobrutinib once daily (QD) from Day 6 to Day 19. On Day 15, Pirtobrutinib was co-administered with 200 mg caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet.
|
|---|---|---|
|
Mean Residence Time (MRT): Caffeine
|
8.58 hour (h)
Geometric Coefficient of Variation 35.8
|
8.03 hour (h)
Geometric Coefficient of Variation 30.9
|
PRIMARY outcome
Timeframe: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose)Population: All participants who received a dose of study drug had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
MRT of Paraxanthine was reported.
Outcome measures
| Measure |
Period 1: Probe Drug Cocktail
n=4 Participants
In period 1, Participants received 200 milligrams (mg) caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet on Day 1.
|
Period 2: Pirtobrutinib + Probe Drug Cocktail
n=4 Participants
In Period 2, Participants received oral dose of 200 mg Pirtobrutinib once daily (QD) from Day 6 to Day 19. On Day 15, Pirtobrutinib was co-administered with 200 mg caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet.
|
|---|---|---|
|
Mean Residence Time (MRT): Paraxanthine
|
12.8 hour (h)
Geometric Coefficient of Variation 18.3
|
10.9 hour (h)
Geometric Coefficient of Variation 14.8
|
PRIMARY outcome
Timeframe: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose)Population: All participants who received a dose of study drug had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
MRT of omeprazole was reported.
Outcome measures
| Measure |
Period 1: Probe Drug Cocktail
n=16 Participants
In period 1, Participants received 200 milligrams (mg) caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet on Day 1.
|
Period 2: Pirtobrutinib + Probe Drug Cocktail
n=16 Participants
In Period 2, Participants received oral dose of 200 mg Pirtobrutinib once daily (QD) from Day 6 to Day 19. On Day 15, Pirtobrutinib was co-administered with 200 mg caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet.
|
|---|---|---|
|
Mean Residence Time (MRT): Omeprazole
|
3.22 hour (h)
Geometric Coefficient of Variation 32.4
|
3.58 hour (h)
Geometric Coefficient of Variation 20.1
|
PRIMARY outcome
Timeframe: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose)Population: All participants who received a dose of study drug had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
MRT of warfarin was reported.
Outcome measures
| Measure |
Period 1: Probe Drug Cocktail
n=16 Participants
In period 1, Participants received 200 milligrams (mg) caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet on Day 1.
|
Period 2: Pirtobrutinib + Probe Drug Cocktail
n=16 Participants
In Period 2, Participants received oral dose of 200 mg Pirtobrutinib once daily (QD) from Day 6 to Day 19. On Day 15, Pirtobrutinib was co-administered with 200 mg caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet.
|
|---|---|---|
|
Mean Residence Time (MRT): Warfarin
|
56.8 hour (h)
Geometric Coefficient of Variation 18.9
|
57.9 hour (h)
Geometric Coefficient of Variation 18.7
|
PRIMARY outcome
Timeframe: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose)Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
t1/2 of caffeine was reported.
Outcome measures
| Measure |
Period 1: Probe Drug Cocktail
n=16 Participants
In period 1, Participants received 200 milligrams (mg) caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet on Day 1.
|
Period 2: Pirtobrutinib + Probe Drug Cocktail
n=16 Participants
In Period 2, Participants received oral dose of 200 mg Pirtobrutinib once daily (QD) from Day 6 to Day 19. On Day 15, Pirtobrutinib was co-administered with 200 mg caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet.
|
|---|---|---|
|
Apparent Terminal Elimination Half-Life (t1/2): Caffeine
|
5.96 hour (h)
Geometric Coefficient of Variation 37.8
|
5.47 hour (h)
Geometric Coefficient of Variation 34.6
|
PRIMARY outcome
Timeframe: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose)Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed. Here 'overall number of participants analyzed' signifies participants with available data for this outcome measure.
t1/2 of Paraxanthine was reported.
Outcome measures
| Measure |
Period 1: Probe Drug Cocktail
n=4 Participants
In period 1, Participants received 200 milligrams (mg) caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet on Day 1.
|
Period 2: Pirtobrutinib + Probe Drug Cocktail
n=4 Participants
In Period 2, Participants received oral dose of 200 mg Pirtobrutinib once daily (QD) from Day 6 to Day 19. On Day 15, Pirtobrutinib was co-administered with 200 mg caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet.
|
|---|---|---|
|
Apparent Terminal Elimination Half-Life (t1/2): Paraxanthine
|
7.17 hour (h)
Geometric Coefficient of Variation 24.0
|
5.79 hour (h)
Geometric Coefficient of Variation 21.8
|
PRIMARY outcome
Timeframe: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose)Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
t1/2 of omeprazole was reported.
Outcome measures
| Measure |
Period 1: Probe Drug Cocktail
n=16 Participants
In period 1, Participants received 200 milligrams (mg) caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet on Day 1.
|
Period 2: Pirtobrutinib + Probe Drug Cocktail
n=16 Participants
In Period 2, Participants received oral dose of 200 mg Pirtobrutinib once daily (QD) from Day 6 to Day 19. On Day 15, Pirtobrutinib was co-administered with 200 mg caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet.
|
|---|---|---|
|
Apparent Terminal Elimination Half-Life (t1/2): Omeprazole
|
1.13 hour (h)
Geometric Coefficient of Variation 48.4
|
1.20 hour (h)
Geometric Coefficient of Variation 37.2
|
PRIMARY outcome
Timeframe: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose)Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
t1/2 of warfarin was reported.
Outcome measures
| Measure |
Period 1: Probe Drug Cocktail
n=16 Participants
In period 1, Participants received 200 milligrams (mg) caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet on Day 1.
|
Period 2: Pirtobrutinib + Probe Drug Cocktail
n=16 Participants
In Period 2, Participants received oral dose of 200 mg Pirtobrutinib once daily (QD) from Day 6 to Day 19. On Day 15, Pirtobrutinib was co-administered with 200 mg caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet.
|
|---|---|---|
|
Apparent Terminal Elimination Half-Life (t1/2): Warfarin
|
43.2 hour (h)
Geometric Coefficient of Variation 17.1
|
42.0 hour (h)
Geometric Coefficient of Variation 16.4
|
Adverse Events
Probe Drug Cocktail
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Pirtobrutinib 200 mg QD
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
Pirtobrutinib 200 mg QD + Probe Drug Cocktail
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Probe Drug Cocktail
n=16 participants at risk
Participants received 200 milligrams (mg) caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet on Day 1.
|
Pirtobrutinib 200 mg QD
n=16 participants at risk
Participants received oral dose of 200 mg Pirtobrutinib once daily (QD) from Day 6 to Day 19.
|
Pirtobrutinib 200 mg QD + Probe Drug Cocktail
n=16 participants at risk
Participant received 200 mg Pirtobrutinib co-administered with 200 mg caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet on Day 15.
|
|---|---|---|---|
|
Gastrointestinal disorders
Cheilitis
|
0.00%
0/16 • From Baseline up to End of Study i.e. 30 days.
All participants who had received at least 1 dose of study drug. Participants were classified into groups based on actual treatment received.
|
6.2%
1/16 • Number of events 1 • From Baseline up to End of Study i.e. 30 days.
All participants who had received at least 1 dose of study drug. Participants were classified into groups based on actual treatment received.
|
0.00%
0/16 • From Baseline up to End of Study i.e. 30 days.
All participants who had received at least 1 dose of study drug. Participants were classified into groups based on actual treatment received.
|
|
General disorders
Vessel puncture site pain
|
0.00%
0/16 • From Baseline up to End of Study i.e. 30 days.
All participants who had received at least 1 dose of study drug. Participants were classified into groups based on actual treatment received.
|
6.2%
1/16 • Number of events 1 • From Baseline up to End of Study i.e. 30 days.
All participants who had received at least 1 dose of study drug. Participants were classified into groups based on actual treatment received.
|
0.00%
0/16 • From Baseline up to End of Study i.e. 30 days.
All participants who had received at least 1 dose of study drug. Participants were classified into groups based on actual treatment received.
|
|
Immune system disorders
Seasonal allergy
|
6.2%
1/16 • Number of events 1 • From Baseline up to End of Study i.e. 30 days.
All participants who had received at least 1 dose of study drug. Participants were classified into groups based on actual treatment received.
|
0.00%
0/16 • From Baseline up to End of Study i.e. 30 days.
All participants who had received at least 1 dose of study drug. Participants were classified into groups based on actual treatment received.
|
0.00%
0/16 • From Baseline up to End of Study i.e. 30 days.
All participants who had received at least 1 dose of study drug. Participants were classified into groups based on actual treatment received.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
6.2%
1/16 • Number of events 1 • From Baseline up to End of Study i.e. 30 days.
All participants who had received at least 1 dose of study drug. Participants were classified into groups based on actual treatment received.
|
0.00%
0/16 • From Baseline up to End of Study i.e. 30 days.
All participants who had received at least 1 dose of study drug. Participants were classified into groups based on actual treatment received.
|
0.00%
0/16 • From Baseline up to End of Study i.e. 30 days.
All participants who had received at least 1 dose of study drug. Participants were classified into groups based on actual treatment received.
|
|
Musculoskeletal and connective tissue disorders
Costochondritis
|
0.00%
0/16 • From Baseline up to End of Study i.e. 30 days.
All participants who had received at least 1 dose of study drug. Participants were classified into groups based on actual treatment received.
|
0.00%
0/16 • From Baseline up to End of Study i.e. 30 days.
All participants who had received at least 1 dose of study drug. Participants were classified into groups based on actual treatment received.
|
6.2%
1/16 • Number of events 1 • From Baseline up to End of Study i.e. 30 days.
All participants who had received at least 1 dose of study drug. Participants were classified into groups based on actual treatment received.
|
|
Nervous system disorders
Dizziness
|
6.2%
1/16 • Number of events 1 • From Baseline up to End of Study i.e. 30 days.
All participants who had received at least 1 dose of study drug. Participants were classified into groups based on actual treatment received.
|
0.00%
0/16 • From Baseline up to End of Study i.e. 30 days.
All participants who had received at least 1 dose of study drug. Participants were classified into groups based on actual treatment received.
|
0.00%
0/16 • From Baseline up to End of Study i.e. 30 days.
All participants who had received at least 1 dose of study drug. Participants were classified into groups based on actual treatment received.
|
|
Nervous system disorders
Headache
|
0.00%
0/16 • From Baseline up to End of Study i.e. 30 days.
All participants who had received at least 1 dose of study drug. Participants were classified into groups based on actual treatment received.
|
6.2%
1/16 • Number of events 1 • From Baseline up to End of Study i.e. 30 days.
All participants who had received at least 1 dose of study drug. Participants were classified into groups based on actual treatment received.
|
0.00%
0/16 • From Baseline up to End of Study i.e. 30 days.
All participants who had received at least 1 dose of study drug. Participants were classified into groups based on actual treatment received.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
6.2%
1/16 • Number of events 1 • From Baseline up to End of Study i.e. 30 days.
All participants who had received at least 1 dose of study drug. Participants were classified into groups based on actual treatment received.
|
6.2%
1/16 • Number of events 1 • From Baseline up to End of Study i.e. 30 days.
All participants who had received at least 1 dose of study drug. Participants were classified into groups based on actual treatment received.
|
0.00%
0/16 • From Baseline up to End of Study i.e. 30 days.
All participants who had received at least 1 dose of study drug. Participants were classified into groups based on actual treatment received.
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
6.2%
1/16 • Number of events 1 • From Baseline up to End of Study i.e. 30 days.
All participants who had received at least 1 dose of study drug. Participants were classified into groups based on actual treatment received.
|
6.2%
1/16 • Number of events 1 • From Baseline up to End of Study i.e. 30 days.
All participants who had received at least 1 dose of study drug. Participants were classified into groups based on actual treatment received.
|
0.00%
0/16 • From Baseline up to End of Study i.e. 30 days.
All participants who had received at least 1 dose of study drug. Participants were classified into groups based on actual treatment received.
|
|
Skin and subcutaneous tissue disorders
Petechiae
|
0.00%
0/16 • From Baseline up to End of Study i.e. 30 days.
All participants who had received at least 1 dose of study drug. Participants were classified into groups based on actual treatment received.
|
31.2%
5/16 • Number of events 5 • From Baseline up to End of Study i.e. 30 days.
All participants who had received at least 1 dose of study drug. Participants were classified into groups based on actual treatment received.
|
0.00%
0/16 • From Baseline up to End of Study i.e. 30 days.
All participants who had received at least 1 dose of study drug. Participants were classified into groups based on actual treatment received.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60