NCT05810740

Bioequivalence Binimetinib 3 x 15 mg and 45 mg Formulations

Completed Phase 1 Results posted Last updated 19 September 2024

What this trial tests

Phase 1 trial testing Binimetinib 15 MG in Melanoma in 37 participants. Completed in 18 January 2023.

Timeline

31 August 2022

Primary endpoint
22 December 2022

18 January 2023

Quick facts

Lead sponsor	Pierre Fabre Medicament
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	crossover
Masking	none
Primary purpose	other
Enrollment	37
Start date	31 August 2022
Primary completion	22 December 2022
Estimated completion	18 January 2023
Sites	1 location across France

Drugs / interventions tested

• Binimetinib 15 MG — full drug profile →
• Binimetinib 45 MG — full drug profile →

Conditions studied

• Melanoma — all drugs for Melanoma →
• BRAF V600 Mutation — all drugs for BRAF V600 Mutation →
• Unresectable Melanoma — all drugs for Unresectable Melanoma →
• Metastatic Melanoma — all drugs for Metastatic Melanoma →

Sponsor

Pierre Fabre Medicament — full company profile →

Who can join

Adults 18 to 65, any sex, with Melanoma or BRAF V600 Mutation. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Area Under the Plasma Concentration-time Curve (AUC) From Time of Administration to Last Observed Plasma Concentration (AUClast) for Binimetinib Primary · 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

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.

Group	Value	95% CI
Reference Formulation	1786	± 23.22
Test Formulation	1723	± 24.13

AUC From Time of Administration to Infinity (AUCinf) for Binimetinib Primary · 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

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

Group	Value	95% CI
Reference Formulation	1834	± 23.09
Test Formulation	1784	± 23.85

Maximum Observed Plasma Concentration (Cmax) for Binimetinib Primary · 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

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.

Group	Value	95% CI
Reference Formulation	388.0	± 46.3
Test Formulation	362.2	± 41.1

Time to Reach Cmax (Tmax) for Binimetinib Secondary · 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

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.

Group	Value	95% CI
Reference Formulation	1.0000	0.500 – 3.000
Test Formulation	0.7500	0.500 – 2.000

Terminal Half-life (t1/2) for Binimetinib Secondary · 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

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

Group	Value	95% CI
Reference Formulation	13.002	± 26.194
Test Formulation	13.901	± 24.696

First Order Terminal Elimination Rate Constant (λz) of Binimetinib Secondary · 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

The first Order Terminal Elimination Rate Constant (λz) of Binimetinib corresponds to the rate at which a drug is removed from the human system

Group	Value	95% CI
Reference Formulation	0.05331	± 26.19381
Test Formulation	0.04986	± 24.69575

Residual Area (AUC_%Extrap_obs) for Binimetinib Secondary · 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

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.

Group	Value	95% CI
Reference Formulation	2.2836	± 53.7862
Test Formulation	2.8499	± 64.4826

Mean Residence Time (MRT) for Binimetinib Secondary · 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

Mean residence time (MRT) is defined as the average time for binimetinib to reside in the body

Group	Value	95% CI
Reference Formulation	11.67	± 22.66
Test Formulation	12.588	± 27.196

Area Under the Plasma Concentration-time Curve (AUC) From Time of Administration to Last Observed Plasma Concentration (AUClast) for AR00426032 Secondary · 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

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

Group	Value	95% CI
Reference Formulation	223.9	± 29.4
Test Formulation	213.5	± 32.0

AUC From Time of Administration to Infinity (AUCinf) for AR00426032 Secondary · 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

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

Group	Value	95% CI
Reference Formulation	296.8	± 18.7
Test Formulation	287.5	± 23.3

Maximum Observed Plasma Concentration (Cmax) for AR00426032 Secondary · 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

Cmax is referred as the maximum observed concentration of AR00426032 in blood plasma determined by bioanalysis

Group	Value	95% CI
Reference Formulation	41.62	± 41.19
Test Formulation	37.88	± 44.25

Time to Reach Cmax (Tmax) for AR00426032 Secondary · 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

The timepoint at which the maximum concentration of AR00426032 is determined by bioanalysis in the blood plasma

Group	Value	95% CI
Reference Formulation	1.1250	0.750 – 5.000
Test Formulation	1.000	0.750 – 3.000

Adverse events — posted to ClinicalTrials.gov

Time frame: 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.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Reference Formulation

Serious: 0/36 (0%)

Deaths: 0/36

Test Formulation

Serious: 0/37 (0%)

Deaths: 0/37

Other adverse events (11 terms — click to expand)

Reaction	System	Reference Formulation	Test Formulation
Covid-19	Infections and infestations	—	—
Tooth abscess	Infections and infestations	—	—
Viral infection	Infections and infestations	—	—
Ocular discomfort	Eye disorders	—	—
Retinal vascular disorder	Eye disorders	—	—
Vision blurred	Eye disorders	—	—
Abdominal pain	Gastrointestinal disorders	—	—
Anal pruritus	Gastrointestinal disorders	—	—
Frequent bowel movements	Gastrointestinal disorders	—	—
Toothache	Gastrointestinal disorders	—	—
Orthostatic hypotension	Vascular disorders	—	—

Data from ClinicalTrials.gov NCT05810740 adverse events section.

Sponsor's own description

The current commercially available MEKTOVI® (binimetinib) 15 mg tablets are provided as immediate release film-coated tablets for oral administration. For the treatment of adult patients with unresectable or metastatic melanoma with BRAF V600 mutation, the recommended dosing regimen is 45 mg twice daily (bis in die, BID). No food effect with the commercial formulation of 15 mg was demonstrated. In order to reduce the patient's burden, a new strength tablet containing 45 mg of binimetinib as active ingredient is being developed. As a result, the number of tablets to be taken by the patients will be reduced from 6 tablets (6 x 15 mg) to 2 tablets (2 x 45 mg) per day. The evaluation of the bioequivalence between one 45 mg tablet and three 15 mg tablets is therefore required.

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.