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

Genentech

Status and phase: Completed; Phase 1

Conditions: Healthy Volunteer

Treatments: Drug: Cobimetinib; Drug: Rabeprazole

Study type: Interventional

Funder types: Industry

Identifiers

NCT01277718

MEK4954g

Details and patient eligibility

About

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.

Enrollment: 20 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion 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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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20 participants in 2 patient groups

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

Experimental group

Description:

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.

Treatment:

Drug: Cobimetinib

Drug: Rabeprazole

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

Experimental group

Description:

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.

Treatment:

Drug: Cobimetinib

Drug: Rabeprazole