Food Effect of VS-6766 in Healthy Adult Subjects

Study Overview
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Brief Summary
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An Open-Label, 2-Way, 2-Period Crossover Study of Orally Administered VS-6766 in Healthy Adult Subjects to Determine the Effect of Food on the Pharmacokinetics of VS-6766

Detailed Description
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This is an open-label, randomized, 2-way, 2-period crossover, Food Effect study. On Day 1 of each period, subjects will receive a single oral dose of VS-6766 administered in a 2-way crossover fashion either under fasting conditions or following a standardized high-fat/high-calorie meal. PK sampling for VS-6766 will be collected predose and postdose. There will be a washout period between doses.

Official Title
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An Open-Label, 2-Way, 2-Period Crossover Study of Orally Administered VS-6766 in Healthy Adult Subjects to Determine the Effect of Food on the Pharmacokinetics of VS-6766

Conditions
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Food Effect

Intervention / Treatment
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* Drug: VS-6766


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy, adult, male or female (of non-childbearing potential only), 18-55 years of age, inclusive, at the screening visit. Must follow protocol specified contraception guidance. Continuous non-smoker who has not used tobacco/nicotine-containing products for at least 3 months prior to the first dosing based on subject self-reporting. Body mass index (BMI) ≥ 18.0 and ≤ 32.0 kg/m2 at the screening visit. Medically healthy with no clinically significant medical history. Able to swallow capsules. Understands the study procedures in the informed consent form (ICF), and be willing and able to comply with the protocol. Exclusion Criteria: Presence of systemic or severe infection. History or presence of a significant medical condition or disease which is not completely resolved. History or presence of alcohol or drug abuse History or presence of hypersensitivity or reaction to the study drug or related compounds. History of tuberculosis. Presence of any fever within 2 weeks prior to first dosing. Females able to have children. Females who are pregnant or lactating. Presence of HIV. Must be able to refrain from using any drugs, including prescription and non-prescription medications beginning 28 days prior to the first dosing. Lactose Intolerance. Donation of blood or significant blood loss or blood transfusion within 56 days prior to the first dosing. Plasma donation within 7 days prior to the first dosing. Participation in another clinical study within 30 days prior to the first dosing.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: This is an open-label, randomized, 2-way, 2-period crossover, Food Effect study.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Treatment A<br>4.0 mg VS-6766, following an overnight fast of at least 10 hours | Drug: VS-6766<br>* Dual RAF/MEK inhibitor<br>|
| Active Comparator: Treatment B<br>4.0 mg VS-6766, administered 30 minutes after the start of a high-fat/high-calorie meal breakfast | Drug: VS-6766<br>* Dual RAF/MEK inhibitor<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Pharmacokinetics (PK) of a single dose of VS-6766 after a standardized high-fat/high-calorie meal and after fasting: AUC0-t | Area under plasma Concentration (AUC) 0 to t | 30 days | 
| Plasma Pharmacokinetics (PK) of a single dose of VS-6766 after a standardized high-fat/high-calorie meal and after fasting: AUC0-120 | Area under plasma Concentration (AUC) from 0-120 minutes | 30 days | 
| Plasma Pharmacokinetics (PK) of a single dose of VS-6766 after a standardized high-fat/high-calorie meal and after fasting: AUC0-inf | Area under plasma Concentration (AUC) from zero to infinity | 30 days | 
| Plasma Pharmacokinetics (PK) of a single dose of VS-6766 after a standardized high-fat/high-calorie meal and after fasting: AUC%extrap | Area under plasma Concentration (AUC) extrapolated | 30 days | 
| Plasma Pharmacokinetics (PK) of a single dose of VS-6766 after a standardized high-fat/high-calorie meal and after fasting: Cmax | Cmax for VS-6766 administered with and without food. | 30 days | 
| Plasma Pharmacokinetics (PK) of a single dose of VS-6766 after a standardized high-fat/high-calorie meal and after fasting: Tlag | absorption lag-time (Tlag) | 30 days | 
| Plasma Pharmacokinetics (PK) of a single dose of VS-6766 after a standardized high-fat/high-calorie meal and after fasting: Tmax | time of Maximum concentration (Tmax) | 30 days | 
| Plasma Pharmacokinetics (PK) of a single dose of VS-6766 after a standardized high-fat/high-calorie meal and after fasting: Kel | Elimination rate (Kel) | 30 days | 
| Plasma Pharmacokinetics (PK) of a single dose of VS-6766 after a standardized high-fat/high-calorie meal and after fasting: T1/2 | concentration Half-life (T1/2) | 30 days | 
| Plasma Pharmacokinetics (PK) of a single dose of VS-6766 after a standardized high-fat/high-calorie meal and after fasting: CL/F | Oral Clearance (CL/F) | 30 days | 
| Plasma Pharmacokinetics (PK) of a single dose of VS-6766 after a standardized high-fat/high-calorie meal and after fasting: Vz/F | Apparent Volume of Distribution (Vz/F) for VS-6766 administered with and without food. | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the safety and tolerability of a single-dose of VS-6766 administered with or without a standardized high-fat/high-calorie meal in healthy adult subjects. | Treatment emergent adverse events/ treatment emergent serious adverse events - their frequency, duration and severity, lab parameters, vital signs, ECG and ophthalmologic changes | 30 days |