Clinical trial NCT01277718: A Study to Evaluate the Effect of a Proton-Pump Inhibitor (Rabeprazole) on the Relative Bioavailability of Cobimetinib in Healthy Participants
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteer
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2011-01-17
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


Eligibility 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)

Primary outcomes:
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of Cobimetinib
timeFrame: Day 1 at 0 hour (predose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 hours postdose
measure: Maximum Observed Concentration of Cobimetinib
timeFrame: Day 1 at 0 hour (predose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 hours postdose
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Genentech, Inc.
name: Isabelle Rooney, M.D., PhD
role: STUDY_DIRECTOR
References: