A Study to Evaluate the Effect of a Proton-Pump Inhibitor (Rabeprazole) on the Relative Bioavailability of Cobimetinib in Healthy Participants
- Registration Number
- NCT01277718
- Lead Sponsor
- Genentech, Inc.
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 20
Inclusion Criteria
Not provided
Exclusion Criteria
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Treatment A first, then Treatment B, followed by Treatment C Rabeprazole 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 A first, then Treatment C, followed by Treatment B Cobimetinib 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 A first, then Treatment B, followed by Treatment C Cobimetinib 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 A first, then Treatment C, followed by Treatment B Rabeprazole 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.
- Primary Outcome Measures
Name Time Method Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) 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 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 Day 1 at 0 hour (predose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 hours postdose
- Secondary Outcome Measures
Name Time Method