MelanomaPhase 1NCT05103891
Relative Bioavailability of Binimetinib 3 x 15 mg and 45 mg Formulations
A Phase 1 study testing Binimetinib Oral Tablet in people with Melanoma and BRAF V600 Mutation, run by Pierre Fabre Medicament at 1 site in France.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Melanoma, BRAF V600 Mutation, Unresectable Melanoma
- What is being tested?
- Binimetinib Oral Tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteFrance
- Study dates
- 3 Sep 2021to 29 Nov 2021
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 14Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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.
- Being tested
- Binimetinib Oral Tablet
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Binimetinib Oral TabletDrug
two-period, crossover study
| Study group | Role | What they receive |
|---|---|---|
| Binimetinib 15 mg / Binimetinib 45 mg | Experimental | 2 periods Receives: Drug: Binimetinib Oral Tablet |
| Binimetinib 45 mg / Binimetinib 15 mg | Experimental | 2 periods Receives: Drug: Binimetinib Oral Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area under the plasma concentration-time curve (AUC) from time of administration to last observed plasma concentration (AUClast)
Measured: Through study completion, an average of 2 months
AUC from time of administration to infinity (AUCinf)
Measured: Through study completion, an average of 2 months
Maximum observed plasma concentration (Cmax)
Measured: Through study completion, an average of 2 months
Time to reach Cmax (Tmax)
Measured: Through study completion, an average of 2 months
AUC Test(T) / Reference (R) ratios
Measured: Through study completion, an average of 2 months
Secondary outcomes (6)
Treatment-emergent adverse events (TEAEs)
Incidence, nature and severity
Measured: Through study completion, an average of 2 months
Treatment-emergent serious adverse events (treatment-emergent SAEs)
Incidence, nature and severity
Measured: Through study completion, an average of 2 months
Electrocardiograms
heart rate (HR), PR interval, QRS duration, QRS axis, QT interval, QTcF
Measured: Through study completion, an average of 2 months
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)
Measured: Through study completion, an average of 2 months
Vital signs
Supine and standing systolic BP, diastolic BP and PR, body temperature
Measured: Through study completion, an average of 2 months
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
Measured: At the screening and at the end of study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Nov 2021
- Study start3 Sep 2021
- Primary completion29 Nov 2021 (estimated)
- Study completion29 Nov 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MelanomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pierre Fabre Medicament
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Biotrial
- Responsible party
- Sponsor
- Investigators
- Marina Klein, MD, Principal investigator, Biotrial
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05103891
- Sponsor's protocol ID
- W00074CI101_1PF73
- Status last verified
- Nov 2021
- First submitted
- 29 Sep 2021
- Last updated
- 1 Dec 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05103891
- Acronym / sponsor ID
- W00074CI101_1PF73
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Pierre Fabre MedicamentIndustry (pharma, biotech, devices)
- Collaborators
- Biotrial
- Study start
- 3 Sep 2021 (actual)
- Primary completion
- 29 Nov 2021 (estimated)
- Study completion
- 29 Nov 2021 (estimated)
- First posted
- 2 Nov 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Binimetinib 15 mg / Binimetinib 45 mg | Experimental | Drug: Binimetinib Oral Tablet2 periods |
| Binimetinib 45 mg / Binimetinib 15 mg | Experimental | Drug: Binimetinib Oral Tablet2 periods |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (14 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Binimetinib Oral Tablettwo-period, crossover study | Drug | Binimetinib 15 mg / Binimetinib 45 mg, Binimetinib 45 mg / Binimetinib 15 mg |
Primary outcome
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
AUC from time of administration to infinity (AUCinf)
Time frame: Through study completion, an average of 2 months
Maximum observed plasma concentration (Cmax)
Time frame: Through study completion, an average of 2 months
Time to reach Cmax (Tmax)
Time frame: Through study completion, an average of 2 months
AUC Test(T) / Reference (R) ratios
Time frame: Through study completion, an average of 2 months
6 secondary outcomes
Treatment-emergent adverse events (TEAEs)
Time frame: 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
Electrocardiograms
Time frame: Through study completion, an average of 2 months
Clinical laboratory parameters
Time frame: Through study completion, an average of 2 months
Vital signs
Time frame: Through study completion, an average of 2 months
Opthalmologic examinations
Time frame: At the screening and at the end of study
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Dec 2021.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marina Klein, MD principal investigator
Biotrial
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Binimetinib Oral Tablet in people with Melanoma and BRAF V600 Mutation, run by Pierre Fabre Medicament at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 1 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Dec 2021.