Trial Outcomes & Findings for Bioequivalence Binimetinib 3 x 15 mg and 45 mg Formulations (NCT NCT05810740)
NCT ID: NCT05810740
Last Updated: 2024-09-19
Results Overview
The AUC is a measure of systemic drug exposure, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample. AUClast is defined as area under the concentration from zero to the last quantifiable plasma concentration.
COMPLETED
PHASE1
37 participants
Pre-dose = 0h and at 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 72 hours post dose
2024-09-19
Participant Flow
Participant milestones
| Measure |
Binimetinib 15 mg Then Binimetinib 45 mg
Participants first received a single dose of 3 tablets of Binimetinib 15 mg orally in fasted conditions in the morning on day 1 of a 5-day period. After a washout period of 7 days, they then received a single dose of 1 tablet of Binimetinib 45 mg orally in fasted conditions in the morning for five days on day 1 of a second 5-day period.
|
Binimetinib 45 mg Then Binimetinib 15 mg
Participants first received a single dose of 1 tablet of Binimetinib 45 mg orally in fasted conditions in the morning on day 1 of a five-day period. After a washout period of 7 days, they then received a single dose of 3 tablets of Binimetinib 15 mg orally in fasted conditions in the morning on day 1 of a second five-day period.
|
|---|---|---|
|
Treatment Period 1 (5 Days)
STARTED
|
19
|
18
|
|
Treatment Period 1 (5 Days)
COMPLETED
|
19
|
18
|
|
Treatment Period 1 (5 Days)
NOT COMPLETED
|
0
|
0
|
|
Washout (7 Days)
STARTED
|
19
|
18
|
|
Washout (7 Days)
COMPLETED
|
19
|
18
|
|
Washout (7 Days)
NOT COMPLETED
|
0
|
0
|
|
Treatment Period 2 (5 Days)
STARTED
|
19
|
18
|
|
Treatment Period 2 (5 Days)
COMPLETED
|
19
|
18
|
|
Treatment Period 2 (5 Days)
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Bioequivalence Binimetinib 3 x 15 mg and 45 mg Formulations
Baseline characteristics by cohort
| Measure |
Binimetinib 15 mg Then Binimetinib 45 mg
n=19 Participants
Participants first received a single dose of 3 tablets of Binimetinib 15 mg orally in fasted conditions in the morning on day 1 of a 5-day period. After a washout period of 7 days, they then received a single dose of 1 tablet of Binimetinib 45 mg orally in fasted conditions in the morning for five days on day 1 of a second 5-day period.
|
Binimetinib 45 mg Then Binimetinib 15 mg
n=18 Participants
Participants first received a single dose of 1 tablet of Binimetinib 45 mg orally in fasted conditions in the morning on day 1 of a five-day period. After a washout period of 7 days, they then received a single dose of 3 tablets of Binimetinib 15 mg orally in fasted conditions in the morning on day 1 of a second five-day period.
|
Total
n=37 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
18 Participants
n=99 Participants
|
18 Participants
n=107 Participants
|
36 Participants
n=206 Participants
|
|
Age, Categorical
>=65 years
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Age, Continuous
|
40.7 years
STANDARD_DEVIATION 14.05 • n=99 Participants
|
43.9 years
STANDARD_DEVIATION 13.35 • n=107 Participants
|
42.3 years
STANDARD_DEVIATION 13.62 • n=206 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
4 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
16 Participants
n=99 Participants
|
17 Participants
n=107 Participants
|
33 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
19 Participants
n=99 Participants
|
18 Participants
n=107 Participants
|
37 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Region of Enrollment
France
|
19 participants
n=99 Participants
|
18 participants
n=107 Participants
|
37 participants
n=206 Participants
|
|
Alcohol history
Never
|
9 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
10 Participants
n=206 Participants
|
|
Alcohol history
Current
|
10 Participants
n=99 Participants
|
17 Participants
n=107 Participants
|
27 Participants
n=206 Participants
|
|
Smoking history
Never
|
11 Participants
n=99 Participants
|
12 Participants
n=107 Participants
|
23 Participants
n=206 Participants
|
|
Smoking history
Former
|
8 Participants
n=99 Participants
|
6 Participants
n=107 Participants
|
14 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Pre-dose = 0h and at 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 72 hours post dosePopulation: The analysis population was the pharmacokinetic set that consisted of 36 healthy participants who had taken one dose of study treatment in the two periods. One participant of the 37 randomised participants was excluded from the pharmacokinetic set due to treatment discontinuation before the second treatment period.
The AUC is a measure of systemic drug exposure, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample. AUClast is defined as area under the concentration from zero to the last quantifiable plasma concentration.
Outcome measures
| Measure |
Reference Formulation
n=36 Participants
Binimetinib 3x15 mg
|
Test Formulation
n=36 Participants
Binimetinib 1x45 mg
|
|---|---|---|
|
Area Under the Plasma Concentration-time Curve (AUC) From Time of Administration to Last Observed Plasma Concentration (AUClast) for Binimetinib
|
1786 h*ng/mL
Geometric Coefficient of Variation 23.22
|
1723 h*ng/mL
Geometric Coefficient of Variation 24.13
|
PRIMARY outcome
Timeframe: Pre-dose = 0h and at 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 72 hours post dosePopulation: The analysis population was the pharmacokinetic set that consisted of 36 healthy participants who had taken one dose of study treatment in the two periods. One participant of the 37 randomised participants was excluded from the pharmacokinetic set due to treatment discontinuation before the second treatment period.
The AUC is a measure of systemic drug exposure, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample. AUCinf is defined as Area under the plasma concentration-time curve from time of administration to infinity
Outcome measures
| Measure |
Reference Formulation
n=36 Participants
Binimetinib 3x15 mg
|
Test Formulation
n=36 Participants
Binimetinib 1x45 mg
|
|---|---|---|
|
AUC From Time of Administration to Infinity (AUCinf) for Binimetinib
|
1834 h*ng/mL
Geometric Coefficient of Variation 23.09
|
1784 h*ng/mL
Geometric Coefficient of Variation 23.85
|
PRIMARY outcome
Timeframe: Pre-dose = 0h and at 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 72 hours post dosePopulation: The analysis population was the pharmacokinetic set that consisted of 36 healthy participants who had taken one dose of study treatment in the two periods. One participant of the 37 randomised participants was excluded from the pharmacokinetic set due to treatment discontinuation before the second treatment period.
Cmax refers to the highest measured drug concentration which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample. Cmax,norm is defined as Cmax divided by dose (mg) per kg body weight.
Outcome measures
| Measure |
Reference Formulation
n=36 Participants
Binimetinib 3x15 mg
|
Test Formulation
n=36 Participants
Binimetinib 1x45 mg
|
|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) for Binimetinib
|
388.0 ng/mL
Geometric Coefficient of Variation 46.3
|
362.2 ng/mL
Geometric Coefficient of Variation 41.1
|
SECONDARY outcome
Timeframe: Pre-dose = 0h and at 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 72 hours post dosePopulation: The analysis population was the pharmacokinetic set that consisted of 36 healthy participants who had taken one dose of study treatment in the two periods. One participant of the 37 randomised participants was excluded from the pharmacokinetic set due to treatment discontinuation before the second treatment period.
Tmax refers to the time after dosing when a drug attains its highest measurable concentration (Cmax). It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content.
Outcome measures
| Measure |
Reference Formulation
n=36 Participants
Binimetinib 3x15 mg
|
Test Formulation
n=36 Participants
Binimetinib 1x45 mg
|
|---|---|---|
|
Time to Reach Cmax (Tmax) for Binimetinib
|
1.0000 h
Interval 0.5 to 3.0
|
0.7500 h
Interval 0.5 to 2.0
|
SECONDARY outcome
Timeframe: Pre-dose = 0h and at 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 72 hours post dosePopulation: The analysis population was the pharmacokinetic set that consisted of 36 healthy participants who had taken one dose of study treatment in the two periods. One participant of the 37 randomised participants was excluded from the pharmacokinetic set due to treatment discontinuation before the second treatment period.
The apparent terminal elimination half-life (t½) is defined as the time necessary for the concentration of a drug to decrease by one-half in the terminal phase
Outcome measures
| Measure |
Reference Formulation
n=36 Participants
Binimetinib 3x15 mg
|
Test Formulation
n=36 Participants
Binimetinib 1x45 mg
|
|---|---|---|
|
Terminal Half-life (t1/2) for Binimetinib
|
13.002 h
Geometric Coefficient of Variation 26.194
|
13.901 h
Geometric Coefficient of Variation 24.696
|
SECONDARY outcome
Timeframe: Pre-dose = 0h and at 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 72 hours post dosePopulation: The analysis population was the pharmacokinetic set that consisted of 36 healthy participants who had taken one dose of study treatment in the two periods. One participant of the 37 randomised participants was excluded from the pharmacokinetic set due to treatment discontinuation before the second treatment period.
The first Order Terminal Elimination Rate Constant (λz) of Binimetinib corresponds to the rate at which a drug is removed from the human system
Outcome measures
| Measure |
Reference Formulation
n=36 Participants
Binimetinib 3x15 mg
|
Test Formulation
n=36 Participants
Binimetinib 1x45 mg
|
|---|---|---|
|
First Order Terminal Elimination Rate Constant (λz) of Binimetinib
|
0.05331 /h
Geometric Coefficient of Variation 26.19381
|
0.04986 /h
Geometric Coefficient of Variation 24.69575
|
SECONDARY outcome
Timeframe: Pre-dose = 0h and at 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 72 hours post dosePopulation: The analysis population was the pharmacokinetic set that consisted of 36 healthy participants who had taken one dose of study treatment in the two periods. One participant of the 37 randomised participants was excluded from the pharmacokinetic set due to treatment discontinuation before the second treatment period.
The residual area under the curve is expressed as a percentage of the total AUC extrapolated from tz to ∞, based on the area under the concentration-time curve.
Outcome measures
| Measure |
Reference Formulation
n=36 Participants
Binimetinib 3x15 mg
|
Test Formulation
n=36 Participants
Binimetinib 1x45 mg
|
|---|---|---|
|
Residual Area (AUC_%Extrap_obs) for Binimetinib
|
2.2836 % of the total AUC
Geometric Coefficient of Variation 53.7862
|
2.8499 % of the total AUC
Geometric Coefficient of Variation 64.4826
|
SECONDARY outcome
Timeframe: Pre-dose = 0h and at 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 72 hours post dosePopulation: The analysis population was the pharmacokinetic set that consisted of 36 healthy participants who had taken one dose of study treatment in the two periods. One participant of the 37 randomised participants was excluded from the pharmacokinetic set due to treatment discontinuation before the second treatment period.
Mean residence time (MRT) is defined as the average time for binimetinib to reside in the body
Outcome measures
| Measure |
Reference Formulation
n=36 Participants
Binimetinib 3x15 mg
|
Test Formulation
n=36 Participants
Binimetinib 1x45 mg
|
|---|---|---|
|
Mean Residence Time (MRT) for Binimetinib
|
11.67 h
Geometric Coefficient of Variation 22.66
|
12.588 h
Geometric Coefficient of Variation 27.196
|
SECONDARY outcome
Timeframe: Pre-dose = 0h and at 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 72 hours post dosePopulation: The analysis population was the pharmacokinetic set that consisted of 36 healthy participants who had taken one dose of study treatment in the two periods. One participant of the 37 randomised participants was excluded from the pharmacokinetic set due to treatment discontinuation before the second treatment period.
The AUC is a measure of systemic drug exposure, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample. AUClast is defined as area under the concentration from zero to the last quantifiable plasma concentration of AR00426032, a metabolite of binimetinib
Outcome measures
| Measure |
Reference Formulation
n=36 Participants
Binimetinib 3x15 mg
|
Test Formulation
n=36 Participants
Binimetinib 1x45 mg
|
|---|---|---|
|
Area Under the Plasma Concentration-time Curve (AUC) From Time of Administration to Last Observed Plasma Concentration (AUClast) for AR00426032
|
223.9 h*ng/mL
Geometric Coefficient of Variation 29.4
|
213.5 h*ng/mL
Geometric Coefficient of Variation 32.0
|
SECONDARY outcome
Timeframe: Pre-dose = 0h and at 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 72 hours post dosePopulation: The analysis population was the pharmacokinetic set that consisted of 36 healthy participants who had taken one dose of study treatment in the two periods. One participant of the 37 randomised participants was excluded from the pharmacokinetic set due to treatment discontinuation before the second treatment period.
The AUC is a measure of systemic drug exposure, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample. AUCinf is defined as Area under the plasma concentration-time curve from time of administration to infinity of AR00426032, a metabolite of binimetinib
Outcome measures
| Measure |
Reference Formulation
n=16 Participants
Binimetinib 3x15 mg
|
Test Formulation
n=18 Participants
Binimetinib 1x45 mg
|
|---|---|---|
|
AUC From Time of Administration to Infinity (AUCinf) for AR00426032
|
296.8 h*ng/mL
Geometric Coefficient of Variation 18.7
|
287.5 h*ng/mL
Geometric Coefficient of Variation 23.3
|
SECONDARY outcome
Timeframe: Pre-dose = 0h and at 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 72 hours post dosePopulation: The analysis population was the pharmacokinetic set that consisted of 36 healthy participants who had taken one dose of study treatment in the two periods. One participant of the 37 randomised participants was excluded from the pharmacokinetic set due to treatment discontinuation before the second treatment period.
Cmax is referred as the maximum observed concentration of AR00426032 in blood plasma determined by bioanalysis
Outcome measures
| Measure |
Reference Formulation
n=36 Participants
Binimetinib 3x15 mg
|
Test Formulation
n=36 Participants
Binimetinib 1x45 mg
|
|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) for AR00426032
|
41.62 ng/mL
Geometric Coefficient of Variation 41.19
|
37.88 ng/mL
Geometric Coefficient of Variation 44.25
|
SECONDARY outcome
Timeframe: Pre-dose = 0h and at 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 72 hours post dosePopulation: The analysis population was the pharmacokinetic set that consisted of 36 healthy participants who had taken one dose of study treatment in the two periods. One participant of the 37 randomised participants was excluded from the pharmacokinetic set due to treatment discontinuation before the second treatment period.
The timepoint at which the maximum concentration of AR00426032 is determined by bioanalysis in the blood plasma
Outcome measures
| Measure |
Reference Formulation
n=36 Participants
Binimetinib 3x15 mg
|
Test Formulation
n=36 Participants
Binimetinib 1x45 mg
|
|---|---|---|
|
Time to Reach Cmax (Tmax) for AR00426032
|
1.1250 h
Interval 0.75 to 5.0
|
1.000 h
Interval 0.75 to 3.0
|
SECONDARY outcome
Timeframe: Pre-dose = 0h and at 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 72 hours post dosePopulation: The analysis population was the pharmacokinetic set that consisted of 36 healthy participants who had taken one dose of study treatment in the two periods. One participant of the 37 randomised participants was excluded from the pharmacokinetic set due to treatment discontinuation before the second treatment period.
The apparent terminal elimination half-life (t½) is defined as the time necessary for the concentration of a drug to decrease by one-half in the terminal phase
Outcome measures
| Measure |
Reference Formulation
n=16 Participants
Binimetinib 3x15 mg
|
Test Formulation
n=18 Participants
Binimetinib 1x45 mg
|
|---|---|---|
|
Terminal Half-life (t1/2) for AR00426032
|
13.924 h
Geometric Coefficient of Variation 24.955
|
13.843 h
Geometric Coefficient of Variation 19.281
|
SECONDARY outcome
Timeframe: Pre-dose = 0h and at 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 72 hours post dosePopulation: The analysis population was the pharmacokinetic set that consisted of 36 healthy participants who had taken one dose of study treatment in the two periods. One participant of the 37 randomised participants was excluded from the pharmacokinetic set due to treatment discontinuation before the second treatment period.
The first Order Terminal Elimination Rate Constant (λz) of AR00426032 corresponds to the rate at which a drug is removed from the human system
Outcome measures
| Measure |
Reference Formulation
n=16 Participants
Binimetinib 3x15 mg
|
Test Formulation
n=18 Participants
Binimetinib 1x45 mg
|
|---|---|---|
|
First Order Terminal Elimination Rate Constant (λz) of AR00426032
|
0.04978 /h
Geometric Coefficient of Variation 24.95496
|
0.05007 /h
Geometric Coefficient of Variation 19.28093
|
SECONDARY outcome
Timeframe: Pre-dose = 0h and at 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 72 hours post dosePopulation: The analysis population was the pharmacokinetic set that consisted of 36 healthy participants who had taken one dose of study treatment in the two periods. One participant of the 37 randomised participants was excluded from the pharmacokinetic set due to treatment discontinuation before the second treatment period.
Mean residence time (MRT) is defined as the average time for AR00426032 to reside in the body
Outcome measures
| Measure |
Reference Formulation
n=16 Participants
Binimetinib 3x15 mg
|
Test Formulation
n=18 Participants
Binimetinib 1x45 mg
|
|---|---|---|
|
Mean Residence Time (MRT) for AR00426032
|
14.900 h
Geometric Coefficient of Variation 23.150
|
14.952 h
Geometric Coefficient of Variation 22.934
|
SECONDARY outcome
Timeframe: Blood samples for hematology parameters were taken at screening, on Day -1 of each period, at H24 and H48 post-dose of each period, and at end of study (EOS)Population: The analysis population was the pharmacokinetic set that consisted of 36 healthy participants who had taken one dose of study treatment in the two periods. One participant of the 37 randomised participants was excluded from the pharmacokinetic set due to treatment discontinuation before the second treatment period.
Clinically significant shift from baseline in blood hematology parameters (Erythrocytes (red blood cells, RBC), hematocrit, hemoglobin, platelets; leukocyte count with differential: basophils, eosinophils, lymphocytes, monocytes, neutrophils/absolute neutrophil count; RBC indices: mean corpuscular hemoglobin, mean corpuscular volume, reticulocytes/erythrocytes.)
Outcome measures
| Measure |
Reference Formulation
n=36 Participants
Binimetinib 3x15 mg
|
Test Formulation
n=37 Participants
Binimetinib 1x45 mg
|
|---|---|---|
|
Clinically Significant Changes From Baseline of Blood Hematology Parameters
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Blood samples for clinical chemistry parameters were taken at screening, on Day -1 of each period, at H24 and H48 post-dose of each period, and at EOSPopulation: The analysis population was the pharmacokinetic set that consisted of 36 healthy participants who had taken one dose of study treatment in the two periods. One participant of the 37 randomised participants was excluded from the pharmacokinetic set due to treatment discontinuation before the second treatment period.
Clinically significant shift from baseline in clinical chemistry parameters (alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), bilirubin, gamma glutamyl transferase (GGT), indirect bilirubin, creatinine, urea, bicarbonate, calcium, chloride, magnesium, potassium, sodium, glucose, cholesterol, urate, albumin, creatine kinase (CK), lactate dehydrogenase, protein, amylase, and lipase)
Outcome measures
| Measure |
Reference Formulation
n=36 Participants
Binimetinib 3x15 mg
|
Test Formulation
n=37 Participants
Binimetinib 1x45 mg
|
|---|---|---|
|
Clinically Significant Changes From Baseline of Clinical Chemistry Parameters
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Blood samples for coagulation parameters were taken at screening, on Day -1 of each period, at H24 and H48 post-dose of each period, and at EOSPopulation: The analysis population was the pharmacokinetic set that consisted of 36 healthy participants who had taken one dose of study treatment in the two periods. One participant of the 37 randomised participants was excluded from the pharmacokinetic set due to treatment discontinuation before the second treatment period.
Clinically significant shifts from baseline in coagulation parameters (activated partial thromboplastin time and prothrombin time)
Outcome measures
| Measure |
Reference Formulation
n=36 Participants
Binimetinib 3x15 mg
|
Test Formulation
n=37 Participants
Binimetinib 1x45 mg
|
|---|---|---|
|
Clinically Significant Changes From Baseline of Coagulation Parameters
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Urinalysis samples were taken at screening, on Day -1 of each period, at H24 and H48 post-dose of each period, and at EOSPopulation: The analysis population was the pharmacokinetic set that consisted of 36 healthy participants who had taken one dose of study treatment in the two periods. One participant of the 37 randomised participants was excluded from the pharmacokinetic set due to treatment discontinuation before the second treatment period.
Clinically significant changes from baseline in the quantitative assessment of pH, bilirubin, erythrocytes, glucose, ketones, leukocyte esterase, nitrite, protein, and urobilinogen
Outcome measures
| Measure |
Reference Formulation
n=36 Participants
Binimetinib 3x15 mg
|
Test Formulation
n=37 Participants
Binimetinib 1x45 mg
|
|---|---|---|
|
Clinically Significant Changes From Baseline of Urinalysis Parameters
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Vital signs were measured at screening, on Day -1 of each period, at Day 1 pre-dose, H24 and H72 post-dose of each period, and at EOSPopulation: The analysis population was the pharmacokinetic set that consisted of 36 healthy participants who had taken one dose of study treatment in the two periods. One participant of the 37 randomised participants was excluded from the pharmacokinetic set due to treatment discontinuation before the second treatment period.
Number of participants with at least one clinically significant vital signs abnormality. The following clinical signs were measured: supine and standing systolic and diastolic blood pressure (mmHg), pulse rate (beats/min) body temperature (°C), body weight, and BMI
Outcome measures
| Measure |
Reference Formulation
n=36 Participants
Binimetinib 3x15 mg
|
Test Formulation
n=37 Participants
Binimetinib 1x45 mg
|
|---|---|---|
|
Clinically Significant Abnormalities Values of Vital Sign Parameters
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Vital signs were measured at screening, on Day -1 of each period, at Day 1 pre-dose, H24 and H72 post-dose of each period, and at EOSPopulation: The analysis population was the pharmacokinetic set that consisted of 36 healthy participants who had taken one dose of study treatment in the two periods. One participant of the 37 randomised participants was excluded from the pharmacokinetic set due to treatment discontinuation before the second treatment period.
The number and percentage of participants with at least one orthostatic hypotension defined as standing systolic blood pressure (SBP) - supine SBP ≤ -20 mmHg or standing diastolic blood pressure (DBP) - supine DBP ≤ -10 mmHg considered clinically significant.
Outcome measures
| Measure |
Reference Formulation
n=36 Participants
Binimetinib 3x15 mg
|
Test Formulation
n=37 Participants
Binimetinib 1x45 mg
|
|---|---|---|
|
Clinically Significant Orthostatic Hypotension
|
0 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: ECG abnormalities were recorded in triplicate at screening, on Day -1 of each period, at Day 1 pre-dose and H24 post-dose of each period, and at EOSPopulation: The analysis population was the pharmacokinetic set that consisted of 36 healthy participants who had taken one dose of study treatment in the two periods. One participant of the 37 randomised participants was excluded from the pharmacokinetic set due to treatment discontinuation before the second treatment period.
Number of participant with at least one clinically significant electrocardiogram abnormality. The following standard 12-lead ECG parameters were recorded: heart rate (beats/min), PR interval (msec), QRS duration (msec), QRS axis (deg), QT interval (msec) and Fridericia QTc interval (msec)
Outcome measures
| Measure |
Reference Formulation
n=36 Participants
Binimetinib 3x15 mg
|
Test Formulation
n=37 Participants
Binimetinib 1x45 mg
|
|---|---|---|
|
Clinically Significant Abnormalities Values in 12-lead Electrocardiograms (ECG)
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: A complete physical examination was performed at screening, on Day -1 of each period, at H24 post-dose of each period, and at EOSPopulation: The analysis population was the pharmacokinetic set that consisted of 36 healthy participants who had taken one dose of study treatment in the two periods. One participant of the 37 randomised participants was excluded from the pharmacokinetic set due to treatment discontinuation before the second treatment period.
Number of participants with at least one clinically significant physical examination abnormality. A complete physical examination, including at minima assessments of the cardiovascular, dermatological, ear/nose/throat, eyes, gastrointestinal, general health/overall appearance, head, lymph, musculoskeletal, neck, neurological, and respiratory systems was performed
Outcome measures
| Measure |
Reference Formulation
n=36 Participants
Binimetinib 3x15 mg
|
Test Formulation
n=37 Participants
Binimetinib 1x45 mg
|
|---|---|---|
|
Clinically Significant Physical Examination Abnormalities
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: A visual examination was performed at Screening at at EOS.Population: The analysis population was the pharmacokinetic set that consisted of 36 healthy participants who had taken one dose of study treatment in the two periods. One participant of the 37 randomised participants was excluded from the pharmacokinetic set due to treatment discontinuation before the second treatment period.
Visual assessment was performed at screening, on Day -1 of each period, at H24 and H72 post-dose of each period, and at EOS
Outcome measures
| Measure |
Reference Formulation
n=36 Participants
Binimetinib 3x15 mg
|
Test Formulation
n=37 Participants
Binimetinib 1x45 mg
|
|---|---|---|
|
Abnormal Changes From Baseline in Visual Examinations
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: An opthalmologic examination was performed at Screening at at EOS.Population: The analysis population was the pharmacokinetic set that consisted of 36 healthy participants who had taken one dose of study treatment in the two periods. One participant of the 37 randomised participants was excluded from the pharmacokinetic set due to treatment discontinuation before the second treatment period.
Abnormal changes from baseline in ophthalmologic examinations including best corrected visual acuity for distance testing, optical coherence tomography and/or fluorescein angiography, slit lamp examination, IOP and dilated fundoscopy with attention to retinal abnormalities
Outcome measures
| Measure |
Reference Formulation
n=36 Participants
Binimetinib 3x15 mg
|
Test Formulation
n=37 Participants
Binimetinib 1x45 mg
|
|---|---|---|
|
Abnormal Changes From Baseline in Ophthalmologic Examinations
|
1 Participants
|
0 Participants
|
Adverse Events
Reference Formulation
Test Formulation
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Reference Formulation
n=36 participants at risk
Binimetinib 3x15 mg
|
Test Formulation
n=37 participants at risk
Binimetinib 1x45 mg
|
|---|---|---|
|
Infections and infestations
Covid-19
|
2.8%
1/36 • Number of events 1 • Adverse events (AEs) were recorded from the time of consent until the end of the follow-up period (up to 30 days after Treatment period 2) and over a total period of 47 days.
AEs were summarized by worst grade according to the NCI-CTCAE V5.0 per participant. The analysis population was the safety set that consisted of the healthy participants who had taken one dose of study treatment in the two periods. One participant of the 37 randomised participants discontinued treatment before the second treatment period and therefore did not receive the reference formulation binimetinib 15 mg.
|
2.7%
1/37 • Number of events 1 • Adverse events (AEs) were recorded from the time of consent until the end of the follow-up period (up to 30 days after Treatment period 2) and over a total period of 47 days.
AEs were summarized by worst grade according to the NCI-CTCAE V5.0 per participant. The analysis population was the safety set that consisted of the healthy participants who had taken one dose of study treatment in the two periods. One participant of the 37 randomised participants discontinued treatment before the second treatment period and therefore did not receive the reference formulation binimetinib 15 mg.
|
|
Infections and infestations
Tooth abscess
|
2.8%
1/36 • Number of events 1 • Adverse events (AEs) were recorded from the time of consent until the end of the follow-up period (up to 30 days after Treatment period 2) and over a total period of 47 days.
AEs were summarized by worst grade according to the NCI-CTCAE V5.0 per participant. The analysis population was the safety set that consisted of the healthy participants who had taken one dose of study treatment in the two periods. One participant of the 37 randomised participants discontinued treatment before the second treatment period and therefore did not receive the reference formulation binimetinib 15 mg.
|
0.00%
0/37 • Adverse events (AEs) were recorded from the time of consent until the end of the follow-up period (up to 30 days after Treatment period 2) and over a total period of 47 days.
AEs were summarized by worst grade according to the NCI-CTCAE V5.0 per participant. The analysis population was the safety set that consisted of the healthy participants who had taken one dose of study treatment in the two periods. One participant of the 37 randomised participants discontinued treatment before the second treatment period and therefore did not receive the reference formulation binimetinib 15 mg.
|
|
Infections and infestations
Viral infection
|
2.8%
1/36 • Number of events 1 • Adverse events (AEs) were recorded from the time of consent until the end of the follow-up period (up to 30 days after Treatment period 2) and over a total period of 47 days.
AEs were summarized by worst grade according to the NCI-CTCAE V5.0 per participant. The analysis population was the safety set that consisted of the healthy participants who had taken one dose of study treatment in the two periods. One participant of the 37 randomised participants discontinued treatment before the second treatment period and therefore did not receive the reference formulation binimetinib 15 mg.
|
0.00%
0/37 • Adverse events (AEs) were recorded from the time of consent until the end of the follow-up period (up to 30 days after Treatment period 2) and over a total period of 47 days.
AEs were summarized by worst grade according to the NCI-CTCAE V5.0 per participant. The analysis population was the safety set that consisted of the healthy participants who had taken one dose of study treatment in the two periods. One participant of the 37 randomised participants discontinued treatment before the second treatment period and therefore did not receive the reference formulation binimetinib 15 mg.
|
|
Eye disorders
Ocular discomfort
|
0.00%
0/36 • Adverse events (AEs) were recorded from the time of consent until the end of the follow-up period (up to 30 days after Treatment period 2) and over a total period of 47 days.
AEs were summarized by worst grade according to the NCI-CTCAE V5.0 per participant. The analysis population was the safety set that consisted of the healthy participants who had taken one dose of study treatment in the two periods. One participant of the 37 randomised participants discontinued treatment before the second treatment period and therefore did not receive the reference formulation binimetinib 15 mg.
|
2.7%
1/37 • Number of events 1 • Adverse events (AEs) were recorded from the time of consent until the end of the follow-up period (up to 30 days after Treatment period 2) and over a total period of 47 days.
AEs were summarized by worst grade according to the NCI-CTCAE V5.0 per participant. The analysis population was the safety set that consisted of the healthy participants who had taken one dose of study treatment in the two periods. One participant of the 37 randomised participants discontinued treatment before the second treatment period and therefore did not receive the reference formulation binimetinib 15 mg.
|
|
Eye disorders
Retinal vascular disorder
|
0.00%
0/36 • Adverse events (AEs) were recorded from the time of consent until the end of the follow-up period (up to 30 days after Treatment period 2) and over a total period of 47 days.
AEs were summarized by worst grade according to the NCI-CTCAE V5.0 per participant. The analysis population was the safety set that consisted of the healthy participants who had taken one dose of study treatment in the two periods. One participant of the 37 randomised participants discontinued treatment before the second treatment period and therefore did not receive the reference formulation binimetinib 15 mg.
|
2.7%
1/37 • Number of events 1 • Adverse events (AEs) were recorded from the time of consent until the end of the follow-up period (up to 30 days after Treatment period 2) and over a total period of 47 days.
AEs were summarized by worst grade according to the NCI-CTCAE V5.0 per participant. The analysis population was the safety set that consisted of the healthy participants who had taken one dose of study treatment in the two periods. One participant of the 37 randomised participants discontinued treatment before the second treatment period and therefore did not receive the reference formulation binimetinib 15 mg.
|
|
Eye disorders
Vision blurred
|
2.8%
1/36 • Number of events 1 • Adverse events (AEs) were recorded from the time of consent until the end of the follow-up period (up to 30 days after Treatment period 2) and over a total period of 47 days.
AEs were summarized by worst grade according to the NCI-CTCAE V5.0 per participant. The analysis population was the safety set that consisted of the healthy participants who had taken one dose of study treatment in the two periods. One participant of the 37 randomised participants discontinued treatment before the second treatment period and therefore did not receive the reference formulation binimetinib 15 mg.
|
0.00%
0/37 • Adverse events (AEs) were recorded from the time of consent until the end of the follow-up period (up to 30 days after Treatment period 2) and over a total period of 47 days.
AEs were summarized by worst grade according to the NCI-CTCAE V5.0 per participant. The analysis population was the safety set that consisted of the healthy participants who had taken one dose of study treatment in the two periods. One participant of the 37 randomised participants discontinued treatment before the second treatment period and therefore did not receive the reference formulation binimetinib 15 mg.
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/36 • Adverse events (AEs) were recorded from the time of consent until the end of the follow-up period (up to 30 days after Treatment period 2) and over a total period of 47 days.
AEs were summarized by worst grade according to the NCI-CTCAE V5.0 per participant. The analysis population was the safety set that consisted of the healthy participants who had taken one dose of study treatment in the two periods. One participant of the 37 randomised participants discontinued treatment before the second treatment period and therefore did not receive the reference formulation binimetinib 15 mg.
|
2.7%
1/37 • Number of events 1 • Adverse events (AEs) were recorded from the time of consent until the end of the follow-up period (up to 30 days after Treatment period 2) and over a total period of 47 days.
AEs were summarized by worst grade according to the NCI-CTCAE V5.0 per participant. The analysis population was the safety set that consisted of the healthy participants who had taken one dose of study treatment in the two periods. One participant of the 37 randomised participants discontinued treatment before the second treatment period and therefore did not receive the reference formulation binimetinib 15 mg.
|
|
Gastrointestinal disorders
Anal pruritus
|
2.8%
1/36 • Number of events 1 • Adverse events (AEs) were recorded from the time of consent until the end of the follow-up period (up to 30 days after Treatment period 2) and over a total period of 47 days.
AEs were summarized by worst grade according to the NCI-CTCAE V5.0 per participant. The analysis population was the safety set that consisted of the healthy participants who had taken one dose of study treatment in the two periods. One participant of the 37 randomised participants discontinued treatment before the second treatment period and therefore did not receive the reference formulation binimetinib 15 mg.
|
0.00%
0/37 • Adverse events (AEs) were recorded from the time of consent until the end of the follow-up period (up to 30 days after Treatment period 2) and over a total period of 47 days.
AEs were summarized by worst grade according to the NCI-CTCAE V5.0 per participant. The analysis population was the safety set that consisted of the healthy participants who had taken one dose of study treatment in the two periods. One participant of the 37 randomised participants discontinued treatment before the second treatment period and therefore did not receive the reference formulation binimetinib 15 mg.
|
|
Gastrointestinal disorders
Frequent bowel movements
|
2.8%
1/36 • Number of events 1 • Adverse events (AEs) were recorded from the time of consent until the end of the follow-up period (up to 30 days after Treatment period 2) and over a total period of 47 days.
AEs were summarized by worst grade according to the NCI-CTCAE V5.0 per participant. The analysis population was the safety set that consisted of the healthy participants who had taken one dose of study treatment in the two periods. One participant of the 37 randomised participants discontinued treatment before the second treatment period and therefore did not receive the reference formulation binimetinib 15 mg.
|
0.00%
0/37 • Adverse events (AEs) were recorded from the time of consent until the end of the follow-up period (up to 30 days after Treatment period 2) and over a total period of 47 days.
AEs were summarized by worst grade according to the NCI-CTCAE V5.0 per participant. The analysis population was the safety set that consisted of the healthy participants who had taken one dose of study treatment in the two periods. One participant of the 37 randomised participants discontinued treatment before the second treatment period and therefore did not receive the reference formulation binimetinib 15 mg.
|
|
Gastrointestinal disorders
Toothache
|
2.8%
1/36 • Number of events 1 • Adverse events (AEs) were recorded from the time of consent until the end of the follow-up period (up to 30 days after Treatment period 2) and over a total period of 47 days.
AEs were summarized by worst grade according to the NCI-CTCAE V5.0 per participant. The analysis population was the safety set that consisted of the healthy participants who had taken one dose of study treatment in the two periods. One participant of the 37 randomised participants discontinued treatment before the second treatment period and therefore did not receive the reference formulation binimetinib 15 mg.
|
0.00%
0/37 • Adverse events (AEs) were recorded from the time of consent until the end of the follow-up period (up to 30 days after Treatment period 2) and over a total period of 47 days.
AEs were summarized by worst grade according to the NCI-CTCAE V5.0 per participant. The analysis population was the safety set that consisted of the healthy participants who had taken one dose of study treatment in the two periods. One participant of the 37 randomised participants discontinued treatment before the second treatment period and therefore did not receive the reference formulation binimetinib 15 mg.
|
|
Vascular disorders
Orthostatic hypotension
|
0.00%
0/36 • Adverse events (AEs) were recorded from the time of consent until the end of the follow-up period (up to 30 days after Treatment period 2) and over a total period of 47 days.
AEs were summarized by worst grade according to the NCI-CTCAE V5.0 per participant. The analysis population was the safety set that consisted of the healthy participants who had taken one dose of study treatment in the two periods. One participant of the 37 randomised participants discontinued treatment before the second treatment period and therefore did not receive the reference formulation binimetinib 15 mg.
|
2.7%
1/37 • Number of events 1 • Adverse events (AEs) were recorded from the time of consent until the end of the follow-up period (up to 30 days after Treatment period 2) and over a total period of 47 days.
AEs were summarized by worst grade according to the NCI-CTCAE V5.0 per participant. The analysis population was the safety set that consisted of the healthy participants who had taken one dose of study treatment in the two periods. One participant of the 37 randomised participants discontinued treatment before the second treatment period and therefore did not receive the reference formulation binimetinib 15 mg.
|
Additional Information
Ana Catarina Pinto, Responsible Medical Officer
Pierre Fabre Médicament
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place