A Study to Evaluate the Effect of a Proton-Pump Inhibitor (Rabeprazole) on the Relative Bioavailability of Cobimetinib in Healthy Participants

A Phase 1, Open-Label, 3-Period, Randomized, Crossover Study to Evaluate the Effect of a Proton-Pump Inhibitor (Rabeprazole) on the Relative Bioavailability of GDC-0973 in Healthy Subjects

This is a Phase 1, single-center, open-label, randomized, 3-period, 2-sequence crossover study of cobimetinib in healthy participants to evaluate the effect of the proton-pump inhibitor (PPI) rabeprazole on the relative bioavailability of cobimetinib in healthy participants when administered in the fed or fasted states.

Study Overview

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

• 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

• With a body mass index range of 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 (does not include alcohol) and at each Check-in
• Negative hepatitis panel (including hepatitis B virus surface antigen [HBsAg] and hepatitis C virus antibody [anti-HCV]) and negative human immunodeficiency virus (HIV) antibody screens
• Healthy males and females of nonchildbearing potential 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/or cholecystectomy will be allowed
• History or presence of an abnormal ECG
• History of alcoholism or drug addiction within 1 year prior to Period 1 Check-in
• Use of any tobacco- or nicotine-containing products within 6 months prior to Period 1 Check-in
• Participation in any other investigational study drug trial in which receipt of an investigational study drug occurred within 30 days or 5 half-lives, whichever is longer, prior to Period 1 Check-in
• Use of any prescription medications/products within 14 days prior to Period 1 Check-in
• Use of any over-the-counter, non-prescription preparations within 7 days prior to Period 1 Check-in
• Use of alcohol-, grapefruit-, or caffeine-containing foods or beverages within 72 hours prior to Period 1 Check-in
• 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
• Use of PPIs or histamine H2 receptor antagonists within 1 month prior to Period 1 Check-in
• Known hypersensitivity to rabeprazole or any of its components or to derived products of benzimidazoles
• Predisposing factors to retinal vein occlusion (RVO)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment A first, then Treatment B, followed by Treatment C; Treatment A in Period 1: One 20-mg tablet of cobimetinib will be administered orally with 240 milliliters (mL) room temperature water after at least an 8-hour fast. Treatment B in Period 2: 20 mg oral rabeprazole will be administered once daily for 4 days starting on Day -4. On Day 1, 20 mg rabeprazole will be administered in fasted state followed by one 20-mg tablet of cobimetinib administration orally with 240 mL room temperature water after at least an 8-hour fast. Treatment C in Period 3: 20 mg oral rabeprazole will be administered once daily for 4 days starting on Day -4. On Day 1, 20 mg rabeprazole will be administered in fasted state. Approximately 30 minutes later, participants will be provided a standardized Food and Drug Administration (FDA) high-fat meal, and approximately 30 minutes after starting meal, one 20-mg tablet of cobimetinib will be administered orally with 240 mL room temperature water. There will be a 13-day washout between cobimetinib doses of each period.	Drug: Cobimetinib; One 20-mg tablet of cobimetinib will be administered orally with 240 mL room temperature water after at least an 8-hour fast or approximately 30 minutes after starting the standardized FDA high-fat meal.; Other Names: GDC-0973; XL518; Drug: Rabeprazole; Rabeprazole 20 mg will be administered orally once daily for 4 days starting on Day -4 and on Day 1 of the treatment period.
Experimental: Treatment A first, then Treatment C, followed by Treatment B; Treatment A in Period 1: One 20-mg tablet of cobimetinib will be administered orally with 240 mL room temperature water after at least an 8-hour fast. Treatment C in Period 2: 20 mg oral rabeprazole will be administered once daily for 4 days starting on Day -4. On Day 1 of the treatment period, 20 mg rabeprazole will be administered in fasted state. Approximately 30 minutes later, participants will be provided a standardized FDA high-fat meal, and approximately 30 minutes after starting meal, one 20-mg tablet of cobimetinib will be administered orally with 240 mL room temperature water. Treatment B in Period 3: 20 mg oral rabeprazole will be administered once daily for 4 days starting on Day -4. On Day 1 of treatment period, 20 mg rabeprazole will be administered in fasted state followed by one 20-mg tablet of cobimetinib administration orally with 240 mL room temperature water after at least an 8-hour fast. There will be a 13-day washout between cobimetinib doses of each period.	Drug: Cobimetinib; One 20-mg tablet of cobimetinib will be administered orally with 240 mL room temperature water after at least an 8-hour fast or approximately 30 minutes after starting the standardized FDA high-fat meal.; Other Names: GDC-0973; XL518; Drug: Rabeprazole; Rabeprazole 20 mg will be administered orally once daily for 4 days starting on Day -4 and on Day 1 of the treatment period.

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) of Cobimetinib	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 Concentration of Cobimetinib		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: January 1, 2011
• Primary Completion (Actual): February 1, 2011
• Study Completion (Actual): February 1, 2011

Study Registration Dates

• First Submitted: January 7, 2011
• First Submitted That Met QC Criteria: January 13, 2011
• First Posted (Estimate): January 17, 2011

Study Record Updates

• Last Update Posted (Actual): May 10, 2017
• Last Update Submitted That Met QC Criteria: April 4, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Rabeprazole
• Other Study ID Numbers: MEK4954g