A Randomized, Phase I, Cross-Over Study to Assess the Relative Bioavailability of Single-Dose Cobimetinib (GDC-0973) in Tablet vs. Capsule Formulation

Study Overview
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Brief Summary
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This study will be a Phase 1, open-label, randomized, 2-period, 2-treatment sequence crossover study to determine the relative bioavailability of cobimetinib administered as a single dose of the tablet formulation relative to a single dose of the capsule formulation to healthy male and female participants. A minimum of 24 participants (12 participants per sequence) will complete the study. Participants will be randomly assigned to 2 possible sequences (i.e., I: A/B, II: B/A) where the treatments are as follows: Treatment A: One cobimetinib tablet administered as a single oral dose after at least an 8-hour fast; Treatment B: Four cobimetinib capsules administered as a single oral dose after at least an 8-hour fast. The study is expected to last approximately 7 weeks.

Official Title
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A PHASE 1, OPEN-LABEL, SINGLE-DOSE, RANDOMIZED, 2-PERIOD, 2-TREATMENT SEQUENCE CROSS-OVER STUDY TO ASSESS THE RELATIVE BIOAVAILABILITY OF COBIMETINIB ADMINISTERED AS A TABLET FORMULATION COMPARED TO A CAPSULE FORMULATION IN HEALTHY SUBJECTS

Conditions
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Healthy Volunteer

Intervention / Treatment
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* Drug: cobimetinib
* Drug: cobimetinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male and female volunteers between 18 and 55 years of age, inclusive Body mass index between 18.5 to 32.0 kg/m2, inclusive; Adequate renal, liver, and hematologic function Participants who are in good health as determined by no clinically significant findings from medical history, 12-lead ECG, vital signs, and clinical laboratory evaluations Exclusion Criteria: Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, or psychiatric disorder (as determined by the Investigator)

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

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Capsule formulation<br> | Drug: cobimetinib<br>* Single, oral dose given as 4 capsules on Day 1 after a minimum 8 h fast<br>* Other names: GDC-0973, XL-518;|
| Experimental: Tablet formulation<br> | Drug: cobimetinib<br>* Single, oral dose given as a tablet on Day 1 after a minimum 8 h fast<br>* Other names: GDC-0973, XL-518;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum observed concentration (Cmax) |  | Days 1 to 10 and 15 to 25 (1 to 10 of the second crossover sequence) | 
| Time to maximum concentration (tmax) |  | Days 1 to 10 and 15 to 25 (1 to 10 of the second crossover sequence) | 
| Area under the concentration-time curve (AUC) |  | Days 1 to 10 and 15 to 25 (1 to 10 of the second crossover sequence) | 
| Apparent terminal elimination rate constant |  | Days 1 to 10 and 15 to 25 (1 to 10 of the second crossover sequence) | 
| Half-life (t1/2) |  | Days 1 to 10 and 15 to 25 (1 to 10 of the second crossover sequence) | 
| Apparent clearance (CL/F) |  | Days 1 to 10 and 15 to 25 (1 to 10 of the second crossover sequence) | 
| Apparent volume of distribution (Vz/F) |  | Days 1 to 10 and 15 to 25 (1 to 10 of the second crossover sequence) | 
| Relative bioavailability (Frel) |  | Days 1 to 10 and 15 to 25 (1 to 10 of the second crossover sequence) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events |  | Up to 4 weeks |