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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteer
• Intervention / Treatment: Drug: cobimetinib; Drug: cobimetinib

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75247

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Genentech, Inc.

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (Actual): May 1, 2014
• Study Completion (Actual): May 1, 2014

Study Registration Dates

• First Submitted: May 9, 2014
• First Submitted That Met QC Criteria: May 9, 2014
• First Posted (Estimate): May 13, 2014

Study Record Updates

• Last Update Posted (Estimate): November 2, 2016
• Last Update Submitted That Met QC Criteria: November 1, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Other Study ID Numbers: GP28370