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Relative Bioavailability of Binimetinib 3 x 15 mg and 45 mg Formulations

Primary Purpose

Melanoma, BRAF V600 Mutation, Unresectable Melanoma

Status

Active

Phase

Phase 1

Locations

France

Study Type

Interventional

Intervention

Binimetinib Oral Tablet

About this trial

This is an interventional other trial for Melanoma

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Healthy participant.
Female participants must be postmenopausal or sterilized.
Body mass index (BMI) of ≥ 18.5 to < 30 kg/m2, with body weight ≥ 50 kg and < 100 kg.
Vital signs within the following ranges or if out of normal ranges, considered as not clinically significant by the Investigator.
Participants must have safety laboratory values within the normal ranges or if out of normal ranges considered as not clinically significant by the Investigator.

Exclusion Criteria:

Pregnant or currently breastfeeding women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test.
A past medical history of clinically significant ECG abnormalities or a family history (grandparents, parents, and siblings) of prolonged QT interval syndrome.
Impaired cardiovascular function.
History of fainting spells or orthostatic hypotension episodes.
Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of drugs or which may jeopardize the participant in case of participation in the study.
History of autonomic dysfunction or Gilbert syndrome.
History or current evidence of Central serous retinopathy (CSR), Retinal vein occlusion (RVO) or ophthalmopathy as assessed by ophthalmologic examination at baseline that would be considered a risk factor for CSR/RVO [e.g., optic disc cupping, visual field defects, intraocular pressure (IOP) > 21 mmHg].
Neuromuscular disorders that were associated with elevated CK (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy).
Smoker or use of tobacco products or products containing nicotine in the last 4 weeks prior to first dosing of study treatment.
Malignancy with the following exceptions:
1. Adequately treated basal cell or squamous cell carcinoma of the skin (adequate wound healing is required prior to study entry).
2. Primary malignancy which had been completely resected and was in complete remission for ≥ 5 years.
History of retinal degenerative disease.
Any vaccination within 4 weeks prior to dosing.

Sites / Locations

Biotrial

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Binimetinib 15 mg / Binimetinib 45 mg

Binimetinib 45 mg / Binimetinib 15 mg

Arm Description

2 periods

Outcomes

Primary Outcome Measures

Area under the plasma concentration-time curve (AUC) from time of administration to last observed plasma concentration (AUClast)

AUC from time of administration to infinity (AUCinf)

Maximum observed plasma concentration (Cmax)

Time to reach Cmax (Tmax)

AUC Test(T) / Reference (R) ratios

Secondary Outcome Measures

Treatment-emergent adverse events (TEAEs)

Incidence, nature and severity

Treatment-emergent serious adverse events (treatment-emergent SAEs)

Incidence, nature and severity

Electrocardiograms

heart rate (HR), PR interval, QRS duration, QRS axis, QT interval, QTcF

Clinical laboratory parameters

Erythrocytes (red blood cells, RBCs), 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, ALT, albumin, ALP, AST, bicarbonate, bilirubin (total and indirect), urea, calcium, chloride, CK, creatinine, amylase, lipase, total cholesterol, glucose, lactate dehydrogenase, magnesium, potassium, sodium, total protein, uric acid, blood pregnancy test (hCG), coagulation (aPTT or PT)

Vital signs

Supine and standing systolic BP, diastolic BP and PR, body temperature

Opthalmologic examinations

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

Full Information

NCT ID

NCT05103891

First Posted

September 29, 2021

Last Updated

November 30, 2021

Sponsor

Pierre Fabre Medicament

Collaborators

Biotrial

1. Study Identification

Unique Protocol Identification Number

NCT05103891

Brief Title

Relative Bioavailability of Binimetinib 3 x 15 mg and 45 mg Formulations

Official Title

A Randomized, Single-center, Open-label, Single Dose, Two-period, Crossover Study to Investigate the Relative Bioavailability of Binimetinib 3 x15 mg and 45 mg Tablets in Healthy Participants

Study Type

Interventional

2. Study Status

Record Verification Date

November 2021

Overall Recruitment Status

Active, not recruiting

Study Start Date

September 3, 2021 (Actual)

Primary Completion Date

November 29, 2021 (Anticipated)

Study Completion Date

November 29, 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Pierre Fabre Medicament

Collaborators

Biotrial

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

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 relative bioavailability of the 45 mg tablet in comparison to three 15 mg tablets intake is therefore required.

Detailed Description

The R formulation is the currently commercially available tablet containing 15 mg of binimetinib as active substance, administered as three tablets for a total of 45 mg binimetinib. The T formulation is the tablet containing 45 mg of binimetinib as active substance in one tablet. Participants will be randomized to one of 2 treatment sequences (RT or TR) containing 2 treatment periods, with at least a 7-day washout between each dose. The study will consist of a screening period between 21 and 2 days before the first study treatment administration on Period (P) 1 Day (D) 1, 2 treatment periods of 5 days each, and a washout of at least 7 days between P1D1 and P2D1. Study treatments are given by the oral route in fasted condition. The end-of-study (EOS) visit will be performed 30 (± 3) days after the last study treatment administration or discontinuation.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Melanoma, BRAF V600 Mutation, Unresectable Melanoma, Metastatic Melanoma

7. Study Design

Primary Purpose

Other

Study Phase

Phase 1

Interventional Study Model

Crossover Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

14 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Binimetinib 15 mg / Binimetinib 45 mg

Arm Type

Experimental

Arm Description

2 periods

Arm Title

Binimetinib 45 mg / Binimetinib 15 mg

Arm Type

Experimental

Arm Description

2 periods

Intervention Type

Drug

Intervention Name(s)

Binimetinib Oral Tablet

Intervention Description

two-period, crossover study

Primary Outcome Measure Information:

Title

Area under the plasma concentration-time curve (AUC) from time of administration to last observed plasma concentration (AUClast)

Time Frame

Through study completion, an average of 2 months

Title

AUC from time of administration to infinity (AUCinf)

Time Frame

Through study completion, an average of 2 months

Title

Maximum observed plasma concentration (Cmax)

Time Frame

Through study completion, an average of 2 months

Title

Time to reach Cmax (Tmax)

Time Frame

Through study completion, an average of 2 months

Title

AUC Test(T) / Reference (R) ratios

Time Frame

Through study completion, an average of 2 months

Secondary Outcome Measure Information:

Title

Treatment-emergent adverse events (TEAEs)

Description

Incidence, nature and severity

Time Frame

Through study completion, an average of 2 months

Title

Treatment-emergent serious adverse events (treatment-emergent SAEs)

Description

Incidence, nature and severity

Time Frame

Through study completion, an average of 2 months

Title

Electrocardiograms

Description

heart rate (HR), PR interval, QRS duration, QRS axis, QT interval, QTcF

Time Frame

Through study completion, an average of 2 months

Title

Clinical laboratory parameters

Description

Time Frame

Through study completion, an average of 2 months

Title

Vital signs

Description

Supine and standing systolic BP, diastolic BP and PR, body temperature

Time Frame

Through study completion, an average of 2 months

Title

Opthalmologic examinations

Description

Time Frame

At the screening and at the end of study

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Healthy participant. Female participants must be postmenopausal or sterilized. Body mass index (BMI) of ≥ 18.5 to < 30 kg/m2, with body weight ≥ 50 kg and < 100 kg. Vital signs within the following ranges or if out of normal ranges, considered as not clinically significant by the Investigator. Participants must have safety laboratory values within the normal ranges or if out of normal ranges considered as not clinically significant by the Investigator. Exclusion Criteria: Pregnant or currently breastfeeding women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test. A past medical history of clinically significant ECG abnormalities or a family history (grandparents, parents, and siblings) of prolonged QT interval syndrome. Impaired cardiovascular function. History of fainting spells or orthostatic hypotension episodes. Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of drugs or which may jeopardize the participant in case of participation in the study. History of autonomic dysfunction or Gilbert syndrome. History or current evidence of Central serous retinopathy (CSR), Retinal vein occlusion (RVO) or ophthalmopathy as assessed by ophthalmologic examination at baseline that would be considered a risk factor for CSR/RVO [e.g., optic disc cupping, visual field defects, intraocular pressure (IOP) > 21 mmHg]. Neuromuscular disorders that were associated with elevated CK (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy). Smoker or use of tobacco products or products containing nicotine in the last 4 weeks prior to first dosing of study treatment. Malignancy with the following exceptions: Adequately treated basal cell or squamous cell carcinoma of the skin (adequate wound healing is required prior to study entry). Primary malignancy which had been completely resected and was in complete remission for ≥ 5 years. History of retinal degenerative disease. Any vaccination within 4 weeks prior to dosing.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Marina Klein, MD

Organizational Affiliation

Biotrial

Official's Role

Principal Investigator

Facility Information:

Facility Name

Biotrial

City

Rennes

ZIP/Postal Code

35000

Country

France

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Relative Bioavailability of Binimetinib 3 x 15 mg and 45 mg Formulations

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