Trial Outcomes & Findings for A Study to Evaluate the Effect of a Proton-Pump Inhibitor (Rabeprazole) on the Relative Bioavailability of Cobimetinib in Healthy Participants (NCT NCT01277718)

Last Updated: 2017-05-10

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

20 participants

Primary outcome timeframe

Day 1 at 0 hour (predose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 hours postdose

Results posted on

2017-05-10

Participant Flow

Participant milestones

Participant milestones
Measure	Treatment A First, Then Treatment B, Followed by Treatment C Treatment A in Period 1: One 20-mg tablet of cobimetinib 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 administered once daily for 4 days starting on Day -4. On Day 1 of the treatment period, 20 mg rabeprazole was administered in fasted state followed by one 20-mg tablet of cobimetinib administered orally with 240 mL room temperature water after at least an 8-hour fast. Treatment C in Period 3: 20 mg oral rabeprazole administered once daily for 4 days starting on Day -4. On Day 1, 20 mg rabeprazole was administered in fasted state. Approximately 30 minutes later, participants were provided a standardized Food and Drug Administration (FDA) high-fat meal, and approximately 30 minutes after starting the meal, one 20-mg tablet of cobimetinib was administered orally with 240 mL room temperature water. There was minimum of a 13-day washout between cobimetinib doses of each period.	Treatment A First, Then Treatment C, Followed by Treatment B Treatment A in Period 1: One 20-mg tablet of cobimetinib administered orally with 240 mL room temperature water after at least an 8-hour fast. Treatment C in Period 2: 20 mg oral rabeprazole administered once daily for 4 days starting on Day -4. On Day 1 of the treatment period, 20 mg rabeprazole was administered in fasted state. Approximately 30 minutes later, participants were provided a standardized FDA high-fat meal, and approximately 30 minutes after starting the meal, one 20-mg tablet of cobimetinib was administered orally with 240 mL room temperature water. Treatment B in Period 3: 20 mg oral rabeprazole administered once daily for 4 days starting on Day -4. On Day 1 of the treatment period, 20 mg rabeprazole was administered in fasted state followed by one 20-mg tablet of cobimetinib administered orally with 240 mL room temperature water after at least an 8-hour fast. There was minimum of a 13-day washout between cobimetinib doses of each period.
Period 1 - First Intervention STARTED	10	10
Period 1 - First Intervention COMPLETED	10	10
Period 1 - First Intervention NOT COMPLETED	0	0
Washout Period of 13 Days STARTED	10	7
Washout Period of 13 Days COMPLETED	10	7
Washout Period of 13 Days NOT COMPLETED	0	0
Period 2 - Second Intervention STARTED	10	10
Period 2 - Second Intervention COMPLETED	10	7
Period 2 - Second Intervention NOT COMPLETED	0	3
Period 3 - Third Intervention STARTED	10	7
Period 3 - Third Intervention COMPLETED	10	7
Period 3 - Third Intervention NOT COMPLETED	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Treatment A First, Then Treatment B, Followed by Treatment C Treatment A in Period 1: One 20-mg tablet of cobimetinib 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 administered once daily for 4 days starting on Day -4. On Day 1 of the treatment period, 20 mg rabeprazole was administered in fasted state followed by one 20-mg tablet of cobimetinib administered orally with 240 mL room temperature water after at least an 8-hour fast. Treatment C in Period 3: 20 mg oral rabeprazole administered once daily for 4 days starting on Day -4. On Day 1, 20 mg rabeprazole was administered in fasted state. Approximately 30 minutes later, participants were provided a standardized Food and Drug Administration (FDA) high-fat meal, and approximately 30 minutes after starting the meal, one 20-mg tablet of cobimetinib was administered orally with 240 mL room temperature water. There was minimum of a 13-day washout between cobimetinib doses of each period.	Treatment A First, Then Treatment C, Followed by Treatment B Treatment A in Period 1: One 20-mg tablet of cobimetinib administered orally with 240 mL room temperature water after at least an 8-hour fast. Treatment C in Period 2: 20 mg oral rabeprazole administered once daily for 4 days starting on Day -4. On Day 1 of the treatment period, 20 mg rabeprazole was administered in fasted state. Approximately 30 minutes later, participants were provided a standardized FDA high-fat meal, and approximately 30 minutes after starting the meal, one 20-mg tablet of cobimetinib was administered orally with 240 mL room temperature water. Treatment B in Period 3: 20 mg oral rabeprazole administered once daily for 4 days starting on Day -4. On Day 1 of the treatment period, 20 mg rabeprazole was administered in fasted state followed by one 20-mg tablet of cobimetinib administered orally with 240 mL room temperature water after at least an 8-hour fast. There was minimum of a 13-day washout between cobimetinib doses of each period.
Period 2 - Second Intervention Protocol Violation	0	1
Period 2 - Second Intervention Physician Decision	0	2

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Entire Study Population n=20 Participants All participants randomized to any treatment.
Age, Continuous	31 years n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants
Sex: Female, Male Male	16 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 1 at 0 hour (predose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 hours postdose

Population: Pharmacokinetic parameters populations included all enrolled participants. Here, number of participants analyzed = participants who were evaluable for this outcome.

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).

Outcome measures

Outcome measures
Measure	Cobimetinib [Fasted] n=20 Participants One 20-mg tablet of cobimetinib administered orally with 240 mL room temperature water after at least an 8-hour fast.	Cobimetinib [Fasted] + Rabeprazole n=16 Participants Participants received 20 mg oral rabeprazole once daily for 4 days starting on Day -4. On Day 1 of the treatment period, 20 mg rabeprazole was administered in fasted state followed by one 20-mg tablet of cobimetinib administered orally with 240 mL room temperature water after at least an 8-hour fast.	Cobimetinib [Fed] + Rabeprazole n=17 Participants Participants received 20 mg oral rabeprazole once daily for 4 days starting on Day -4. On Day 1 of the treatment period, 20 mg rabeprazole was administered in fasted state. Approximately 30 minutes later, participants were provided a standardized FDA high-fat meal, and approximately 30 minutes after starting the meal, one 20-mg tablet of cobimetinib was administered orally with 240 mL room temperature water.
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of Cobimetinib	778 nanogramshours/milliliter (nghr/mL) Geometric Coefficient of Variation 32.8	864 nanogramshours/milliliter (nghr/mL) Geometric Coefficient of Variation 39.1	846 nanogramshours/milliliter (nghr/mL) Geometric Coefficient of Variation 48.2

PRIMARY outcome

Timeframe: Day 1 at 0 hour (predose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 hours postdose

Population: Pharmacokinetic parameters populations included all enrolled participants. Here, number of participants analyzed = participants who were evaluable for this outcome.

Outcome measures

Outcome measures
Measure	Cobimetinib [Fasted] n=20 Participants One 20-mg tablet of cobimetinib administered orally with 240 mL room temperature water after at least an 8-hour fast.	Cobimetinib [Fasted] + Rabeprazole n=17 Participants Participants received 20 mg oral rabeprazole once daily for 4 days starting on Day -4. On Day 1 of the treatment period, 20 mg rabeprazole was administered in fasted state followed by one 20-mg tablet of cobimetinib administered orally with 240 mL room temperature water after at least an 8-hour fast.	Cobimetinib [Fed] + Rabeprazole n=17 Participants Participants received 20 mg oral rabeprazole once daily for 4 days starting on Day -4. On Day 1 of the treatment period, 20 mg rabeprazole was administered in fasted state. Approximately 30 minutes later, participants were provided a standardized FDA high-fat meal, and approximately 30 minutes after starting the meal, one 20-mg tablet of cobimetinib was administered orally with 240 mL room temperature water.
Maximum Observed Concentration of Cobimetinib	17.0 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 35.3	17.2 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 36.0	14.8 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 51.2

Adverse Events

Cobimetinib [Fasted]

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Cobimetinib [Fasted] + Rabeprazole

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Cobimetinib [Fed] + Rabeprazole

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800-821-8590

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER

Other adverse events
Measure	Cobimetinib [Fasted] n=20 participants at risk One 20-mg tablet of cobimetinib administered orally with 240 mL room temperature water after at least an 8-hour fast.	Cobimetinib [Fasted] + Rabeprazole n=17 participants at risk Participants received 20 mg oral rabeprazole once daily for 4 days starting on Day -4. On Day 1 of the treatment period, 20 mg rabeprazole was administered in fasted state followed by one 20-mg tablet of cobimetinib administered orally with 240 mL room temperature water after at least an 8-hour fast.	Cobimetinib [Fed] + Rabeprazole n=20 participants at risk Participants received 20 mg oral rabeprazole once daily for 4 days starting on Day -4. On Day 1 of the treatment period, 20 mg rabeprazole was administered in fasted state. Approximately 30 minutes later, participants were provided a standardized FDA high-fat meal, and approximately 30 minutes after starting the meal, one 20-mg tablet of cobimetinib was administered orally with 240 mL room temperature water.
Gastrointestinal disorders Nausea	0.00% 0/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	11.8% 2/17 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	10.0% 2/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.
Gastrointestinal disorders Diarrhoea	0.00% 0/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	0.00% 0/17 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	10.0% 2/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.
Gastrointestinal disorders Vomiting	0.00% 0/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	0.00% 0/17 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	10.0% 2/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.
Gastrointestinal disorders Abdominal pain	0.00% 0/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	0.00% 0/17 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	5.0% 1/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.
Gastrointestinal disorders Abdominal pain lower	5.0% 1/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	0.00% 0/17 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	0.00% 0/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.
Gastrointestinal disorders Flatulence	0.00% 0/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	0.00% 0/17 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	5.0% 1/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.
Infections and infestations Gastroenteritis viral	0.00% 0/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	5.9% 1/17 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	5.0% 1/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.
Infections and infestations Oral herpes	0.00% 0/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	5.9% 1/17 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	0.00% 0/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.
Infections and infestations Respiratory tract infection viral	5.0% 1/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	0.00% 0/17 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	0.00% 0/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.
Infections and infestations Upper respiratory tract Infection	5.0% 1/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	0.00% 0/17 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	0.00% 0/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.
Infections and infestations Viral pharyngitis	0.00% 0/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	0.00% 0/17 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	5.0% 1/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.
Infections and infestations Viral upper respiratory tract infection	5.0% 1/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	0.00% 0/17 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	0.00% 0/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	11.8% 2/17 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	5.0% 1/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	0.00% 0/17 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	5.0% 1/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	5.9% 1/17 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	0.00% 0/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	5.9% 1/17 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	0.00% 0/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	0.00% 0/17 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	5.0% 1/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.
Nervous system disorders Headache	10.0% 2/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	11.8% 2/17 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	10.0% 2/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.
Nervous system disorders Dizziness	0.00% 0/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	11.8% 2/17 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	10.0% 2/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.
Nervous system disorders Depressed level of consciousness	0.00% 0/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	0.00% 0/17 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	5.0% 1/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.
Eye disorders Eye irritation	5.0% 1/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	0.00% 0/17 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	0.00% 0/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.
Eye disorders Eye pain	0.00% 0/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	5.9% 1/17 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	0.00% 0/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.
Eye disorders Ocular hyperaemia	0.00% 0/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	0.00% 0/17 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	5.0% 1/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.
Eye disorders Photophobia	0.00% 0/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	5.9% 1/17 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	0.00% 0/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.
Eye disorders Scleral hyperaemia	0.00% 0/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	5.9% 1/17 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	0.00% 0/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.
Eye disorders Vision blurred	0.00% 0/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	5.9% 1/17 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	0.00% 0/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.
General disorders Chills	0.00% 0/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	0.00% 0/17 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	10.0% 2/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.
General disorders Asthenia	0.00% 0/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	5.9% 1/17 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	0.00% 0/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.
General disorders Feeling cold	0.00% 0/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	0.00% 0/17 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	5.0% 1/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.
General disorders Vessel puncture site haematoma	5.0% 1/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	0.00% 0/17 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	0.00% 0/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.
Ear and labyrinth disorders Hyperacusis	0.00% 0/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	5.9% 1/17 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	0.00% 0/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.
Ear and labyrinth disorders Vertigo	0.00% 0/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	5.9% 1/17 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	0.00% 0/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.
Injury, poisoning and procedural complications Muscle strain	0.00% 0/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	0.00% 0/17 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	5.0% 1/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.
Injury, poisoning and procedural complications Skin laceration	0.00% 0/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	5.9% 1/17 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	0.00% 0/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.
Psychiatric disorders Insomnia	5.0% 1/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	5.9% 1/17 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	0.00% 0/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.
Reproductive system and breast disorders Dysmenorrhoea	0.00% 0/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	5.9% 1/17 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	5.0% 1/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.
Skin and subcutaneous tissue disorders Papule	5.0% 1/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	0.00% 0/17 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	0.00% 0/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.
Skin and subcutaneous tissue disorders Pruritus	5.0% 1/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	0.00% 0/17 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	0.00% 0/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.
Skin and subcutaneous tissue disorders Rash	0.00% 0/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	0.00% 0/17 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	5.0% 1/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.
Blood and lymphatic system disorders Lymphadenopathy	5.0% 1/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	0.00% 0/17 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.	0.00% 0/20 • Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days) Three participants discontinued study in second period and did not receive Cobimetinib \[Fasted\] + Rabeprazole in third period. Therefore, only 17 participants were evaluable for adverse events in the Cobimetinib \[Fasted\] + Rabeprazole treatment arm.