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

NCT05103891 | Unknown Phase 1

• 1 other identifier: W00074CI101_1PF73
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

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.

Conditions

Melanoma; BRAF V600 Mutation; Unresectable Melanoma; Metastatic Melanoma

Outcome Measures

Primary Outcomes (5)

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

  Through study completion, an average of 2 months

• AUC from time of administration to infinity (AUCinf)

  Through study completion, an average of 2 months

• Maximum observed plasma concentration (Cmax)

  Through study completion, an average of 2 months

• Time to reach Cmax (Tmax)

  Through study completion, an average of 2 months

• AUC Test(T) / Reference (R) ratios

  Through study completion, an average of 2 months

Secondary Outcomes (6)

• Treatment-emergent adverse events (TEAEs)

  Through study completion, an average of 2 months

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

  Through study completion, an average of 2 months

• Electrocardiograms

  Through study completion, an average of 2 months

• Clinical laboratory parameters

  Through study completion, an average of 2 months

• Vital signs

  Through study completion, an average of 2 months

Study Arms (2)

Binimetinib 15 mg / Binimetinib 45 mg

EXPERIMENTAL

2 periods

Drug: Binimetinib Oral Tablet

Binimetinib 45 mg / Binimetinib 15 mg

EXPERIMENTAL

2 periods

Drug: Binimetinib Oral Tablet

Interventions

Binimetinib Oral Tablet DRUG

two-period, crossover study

Binimetinib 15 mg / Binimetinib 45 mg; Binimetinib 45 mg / Binimetinib 15 mg

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pierre Fabre Medicament: lead
• Biotrial: collaborator

Study Sites (1)

Biotrial

Rennes, 35000, France

Location

MeSH Terms

Conditions

Melanoma

Interventions

binimetinib

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Marina Klein, MD

  Biotrial

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 29, 2021
• First Posted: November 2, 2021
• Study Start: September 3, 2021
• Primary Completion: November 29, 2021
• Study Completion: November 29, 2021
• Last Updated: December 1, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)