A Study of Relative Bioavailability and Food Effect Study of Cobimetinib in Healthy Participants

A Phase I, Single-Dose, Randomized, Cross-Over, Relative Bioavailability, and Food Effect Study of GDC-0973 in Healthy Subjects

This study will be an open-label, randomized, 3-way, 6-sequence crossover study in healthy participants for determining the relative bioavailability of the tablet formulation to the capsule formulation and the effect of food on the relative bioavailability of the tablet formulation.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Cobimetinib

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

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

• Within body mass index range 18.5 to 29.9 kilograms per meter square (kg/m^2)
• In good health, determined by no clinically significant findings from medical history, 12-lead electrocardiogram (ECG) and vital signs
• Clinical laboratory evaluations within the reference range for the test laboratory
• Negative test for selected drugs of abuse at Screening and at each Check-in
• Negative hepatitis panel and anti-hepatitis C virus and negative human immunodeficiency virus (HIV) antibody screens
• Healthy males and females of non-child-bearing potential or who agree to use effective contraception

Exclusion Criteria

• Significant history or clinical manifestation of any significant metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, or psychiatric disorder
• History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance
• History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs except that appendectomy, hernia repair, and cholecystectomy will be allowed
• History or presence of an abnormal ECG
• History of alcoholism or drug addiction prior to study start
• Use of any tobacco-containing or nicotine-containing products prior to study start
• Participation in any other investigational study drug trial in which receipt of an investigational study drug occurred within 28 days or 5 half-lives, whichever is longer, prior to study start
• Use of any prescription medications/products, including proton pump inhibitors, within 14 days prior to study start
• Poor peripheral venous access
• Any acute or chronic condition that would limit the participant's ability to complete and/or participate in this clinical study
• Female participant is pregnant, lactating, or breastfeeding
• Predisposing factors to retinal vein occlusion (RVO)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment A first, then Treatment B, followed by Treatment C; Treatment A: One 20-mg tablet of cobimetinib will be administered orally with 240 milliliter (mL) room temperature water after at least an 8-hour fast, in first intervention period. Treatment B: Four 5-mg capsules of cobimetinib will be administered orally with 240 mL room temperature water after at least an 8-hour fast, in second intervention period. Treatment C: One 20-mg tablet of cobimetinib will be administered orally with 240 mL room temperature water within 30 minutes of eating a standard Food and Drug Administration (FDA) high-fat meal, in third intervention period. The washout period between each period will be a minimum of 10 days.	Drug: Cobimetinib; Cobimetinib 20 mg will be given orally as tablet formulation in fasted or fed state, or as capsule formulation in fasted state.; Other Names: GDC-0973; XL518
Experimental: Treatment A first, then Treatment C, followed by Treatment B; Treatment A: One 20-mg tablet of cobimetinib will be administered orally with 240 mL room temperature water after at least an 8-hour fast, in first intervention period. Treatment C: One 20-mg tablet of cobimetinib will be administered orally with 240 mL room temperature water within 30 minutes of eating a standard FDA high-fat meal, in second intervention period. Treatment B: Four 5-mg capsules of cobimetinib administered will be orally with 240 mL room temperature water after at least an 8-hour fast, in third intervention period.	Drug: Cobimetinib; Cobimetinib 20 mg will be given orally as tablet formulation in fasted or fed state, or as capsule formulation in fasted state.; Other Names: GDC-0973; XL518
Experimental: Treatment B first, then Treatment A, followed by Treatment C; Treatment B: Four 5-mg capsules of cobimetinib will be administered orally with 240 mL room temperature water after at least an 8-hour fast, in first intervention period. Treatment A: One 20-mg tablet of cobimetinib will be administered orally with 240 mL room temperature water after at least an 8-hour fast, in second intervention period. Treatment C: One 20-mg tablet of cobimetinib will be administered orally with 240 mL room temperature water within 30 minutes of eating a standard FDA high-fat meal, in third intervention period.	Drug: Cobimetinib; Cobimetinib 20 mg will be given orally as tablet formulation in fasted or fed state, or as capsule formulation in fasted state.; Other Names: GDC-0973; XL518
Experimental: Treatment B first, then Treatment C, followed by Treatment A; Treatment B: Four 5-mg capsules of cobimetinib will be administered orally with 240 mL room temperature water after at least an 8-hour fast, in first intervention period. Treatment C: One 20-mg tablet of cobimetinib will be administered orally with 240 mL room temperature water within 30 minutes of eating a standard FDA high-fat meal, in second intervention period. Treatment A: One 20-mg tablet of cobimetinib will be administered orally with 240 mL room temperature water after at least an 8-hour fast, in third intervention period.	Drug: Cobimetinib; Cobimetinib 20 mg will be given orally as tablet formulation in fasted or fed state, or as capsule formulation in fasted state.; Other Names: GDC-0973; XL518
Experimental: Treatment C first, then Treatment A, followed by Treatment B; Treatment C: One 20-mg tablet of cobimetinib will be administered orally with 240 mL room temperature water within 30 minutes of eating a standard FDA high-fat meal, in first intervention period. Treatment A: One 20-mg tablet of cobimetinib will be administered orally with 240 mL room temperature water after at least an 8-hour fast, in second intervention period. Treatment B: Four 5-mg capsules of cobimetinib will be administered orally with 240 mL room temperature water after at least an 8-hour fast, in third intervention period.	Drug: Cobimetinib; Cobimetinib 20 mg will be given orally as tablet formulation in fasted or fed state, or as capsule formulation in fasted state.; Other Names: GDC-0973; XL518
Experimental: Treatment C first, then Treatment B, followed by Treatment A; Treatment C: One 20-mg tablet of cobimetinib will be administered orally with 240 mL room temperature water within 30 minutes of eating a standard FDA high-fat meal, in first intervention period. Treatment B: Four 5-mg capsules of cobimetinib will be administered orally with 240 mL room temperature water after at least an 8-hour fast, in second intervention period. Treatment A: One 20-mg tablet of cobimetinib will be administered orally with 240 mL room temperature water after at least an 8-hour fast, in third intervention period.	Drug: Cobimetinib; Cobimetinib 20 mg will be given orally as tablet formulation in fasted or fed state, or as capsule formulation in fasted state.; Other Names: GDC-0973; XL518

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf)	AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - inf). It is obtained from AUC (0 - t) plus AUC (t - inf).	Day 1 at 0 hour (predose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 hours postdose
Maximum Observed Plasma Concentration (Cmax)		Day 1 at 0 hour (predose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 hours postdose
Minimum Observed Plasma Concentration (Cmin)		Day 1 at 0 hour (predose)
Apparent Oral Clearance (CL/F)	Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.	Day 1 at 0 hour (predose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 hours postdose
Apparent Volume of Distribution (V/F)	Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.	Day 1 at 0 hour (predose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 hours postdose

Collaborators and Investigators

• Sponsor: Genentech, Inc.
• Investigators: Study Director: Isabelle Rooney, M.D., PhD, Genentech, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2010
• Primary Completion (Actual): January 10, 2011
• Study Completion (Actual): January 10, 2011

Study Registration Dates

• First Submitted: November 24, 2010
• First Submitted That Met QC Criteria: November 24, 2010
• First Posted (Estimate): November 29, 2010

Study Record Updates

• Last Update Posted (Actual): August 15, 2017
• Last Update Submitted That Met QC Criteria: July 6, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Other Study ID Numbers: MEK4953g