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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.
ClinicalTrials.gov Identifier:
NCT01277718
First received: January 7, 2011
Last updated: May 27, 2016
Last verified: May 2016
  Purpose
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.

Condition Intervention Phase
Healthy Volunteer
Drug: Cobimetinib
Drug: Rabeprazole
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-availability Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Genentech, Inc.:

Primary Outcome Measures:
  • Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of Cobimetinib [ Time Frame: Day 1 at 0 hour (predose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 hours postdose ] [ Designated as safety issue: No ]
    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).

  • Maximum Observed Concentration of Cobimetinib [ Time Frame: Day 1 at 0 hour (predose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 hours postdose ] [ Designated as safety issue: No ]

Enrollment: 20
Study Start Date: January 2011
Study Completion Date: February 2011
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01277718

Sponsors and Collaborators
Genentech, Inc.
Investigators
Study Director: Isabelle Rooney, M.D., PhD Genentech, Inc.
  More Information

Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT01277718     History of Changes
Other Study ID Numbers: MEK4954g 
Study First Received: January 7, 2011
Results First Received: May 27, 2016
Last Updated: May 27, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Rabeprazole
Proton Pump Inhibitors
Anti-Ulcer Agents
Gastrointestinal Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on December 02, 2016