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

NCT01277718 | Completed Phase 1 Results

• 1 other identifier: MEK4954g
• Study Type: interventional
• Target: 20
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Healthy Volunteer

Outcome Measures

Primary Outcomes (2)

• 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

Study Arms (2)

Treatment A first, then Treatment B, followed by Treatment C

EXPERIMENTAL

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; Drug: Rabeprazole

Treatment A first, then Treatment C, followed by Treatment B

EXPERIMENTAL

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; Drug: Rabeprazole

Interventions

Cobimetinib DRUG

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.

Also known as: GDC-0973, XL518

Treatment A first, then Treatment B, followed by Treatment C; Treatment A first, then Treatment C, followed by Treatment B

Rabeprazole DRUG

Rabeprazole 20 mg will be administered orally once daily for 4 days starting on Day -4 and on Day 1 of the treatment period.

Treatment A first, then Treatment B, followed by Treatment C; Treatment A first, then Treatment C, followed by Treatment B

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Genentech, Inc.: lead

MeSH Terms

Interventions

cobimetinib; Rabeprazole

Intervention Hierarchy (Ancestors)

2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800-821-8590

Study Officials

• Isabelle Rooney, M.D., PhD

  Genentech, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 7, 2011
• First Posted: January 17, 2011
• Study Start: January 1, 2011
• Primary Completion: February 1, 2011
• Study Completion: February 1, 2011
• Last Updated: May 10, 2017
• Results First Posted: July 7, 2016

Record last verified: 2017-04