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

November 30, 2021 updated by: Pierre Fabre Medicament

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
14

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Rennes, France, 35000
        • Biotrial

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Healthy participant.
  2. Female participants must be postmenopausal or sterilized.
  3. Body mass index (BMI) of ≥ 18.5 to < 30 kg/m2, with body weight ≥ 50 kg and < 100 kg.
  4. Vital signs within the following ranges or if out of normal ranges, considered as not clinically significant by the Investigator.
  5. 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:

  1. 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.
  2. A past medical history of clinically significant ECG abnormalities or a family history (grandparents, parents, and siblings) of prolonged QT interval syndrome.
  3. Impaired cardiovascular function.
  4. History of fainting spells or orthostatic hypotension episodes.
  5. 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.
  6. History of autonomic dysfunction or Gilbert syndrome.
  7. 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].
  8. Neuromuscular disorders that were associated with elevated CK (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy).
  9. Smoker or use of tobacco products or products containing nicotine in the last 4 weeks prior to first dosing of study treatment.

  10. 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.
  11. History of retinal degenerative disease.
  12. Any vaccination within 4 weeks prior to dosing.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Binimetinib 15 mg / Binimetinib 45 mg
2 periods
Drug: Binimetinib Oral Tablet
two-period, crossover study
Experimental: Binimetinib 45 mg / Binimetinib 15 mg
2 periods
Drug: Binimetinib Oral Tablet
two-period, crossover study

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
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
Through study completion, an average of 2 months
AUC from time of administration to infinity (AUCinf)
Time Frame: Through study completion, an average of 2 months
Through study completion, an average of 2 months
Maximum observed plasma concentration (Cmax)
Time Frame: Through study completion, an average of 2 months
Through study completion, an average of 2 months
Time to reach Cmax (Tmax)
Time Frame: Through study completion, an average of 2 months
Through study completion, an average of 2 months
AUC Test(T) / Reference (R) ratios
Time Frame: Through study completion, an average of 2 months
Through study completion, an average of 2 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Treatment-emergent adverse events (TEAEs)
Time Frame: Through study completion, an average of 2 months
Incidence, nature and severity
Through study completion, an average of 2 months
Treatment-emergent serious adverse events (treatment-emergent SAEs)
Time Frame: Through study completion, an average of 2 months
Incidence, nature and severity
Through study completion, an average of 2 months
Electrocardiograms
Time Frame: Through study completion, an average of 2 months
heart rate (HR), PR interval, QRS duration, QRS axis, QT interval, QTcF
Through study completion, an average of 2 months
Clinical laboratory parameters
Time Frame: Through study completion, an average of 2 months
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)
Through study completion, an average of 2 months
Vital signs
Time Frame: Through study completion, an average of 2 months
Supine and standing systolic BP, diastolic BP and PR, body temperature
Through study completion, an average of 2 months
Opthalmologic examinations
Time Frame: At the screening and at the end of study
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
At the screening and at the end of study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Pierre Fabre Medicament

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Biotrial

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Marina Klein, MD, Biotrial

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 3, 2021

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 29, 2021

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 29, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 29, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 22, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 2, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 1, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 30, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • W00074CI101_1PF73

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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