Healthy VolunteerPhase 1NCT01277718

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

A Phase 1 study testing Cobimetinib and Rabeprazole in people with Healthy Volunteer, run by Genentech, Inc..

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial 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… Read more about this study

Who is it for?: Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for: Healthy Volunteer
What is being tested?: Cobimetinib and Rabeprazole
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 20 participants
Where: No sites listed yet
Study dates: Jan 2011to Feb 2011
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 55 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

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

Who cannot join

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

Show all 16Show fewer

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)

About this study

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

Conditions: Healthy Volunteer
Being tested: Cobimetinib, Rabeprazole

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

CobimetinibDrug
Also called GDC-0973, XL518
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.
RabeprazoleDrug
Rabeprazole 20 mg will be administered orally once daily for 4 days starting on Day -4 and on Day 1 of the treatment period.

Study groups in NCT01277718
Study group	Role	What they receive
Treatment A first, then Treatment B, followed by Treatment C	Experimental	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. Receives: Drug: Cobimetinib; Drug: Rabeprazole
Treatment A first, then Treatment C, followed by Treatment B	Experimental	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. Receives: Drug: Cobimetinib; Drug: Rabeprazole

What is being measured

The primary outcome is the main question the study is designed to answer.

Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of Cobimetinib
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).
Measured: Day 1 at 0 hour (predose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 hours postdose
Maximum Observed Concentration of Cobimetinib
Measured: Day 1 at 0 hour (predose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 hours postdose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jan 2011Feb 2011

First posted17 Jan 2011 (estimated)
Study startJan 2011
Primary completionFeb 2011
Study completionFeb 2011

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Healthy VolunteerStudies of the same condition, open and under way.
More trials run by Genentech, Inc.The sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Enrolment: 20 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01277718
Sponsor's protocol ID: MEK4954g
Status last verified: Apr 2017
First submitted: 7 Jan 2011
Last updated: 10 May 2017
Results posted: Yes, on ClinicalTrials.gov

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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All Healthy Volunteer trials

Study at a glance

From the registry record, last updated by the sponsor on 10 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT01277718
Acronym / sponsor ID: MEK4954g
Conditions: Healthy Volunteer
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 20 participants (actual)
Lead sponsor: Genentech, Inc.Industry (pharma, biotech, devices)
Study start: Jan 2011
Primary completion: Feb 2011 (actual)
Study completion: Feb 2011 (actual)
First posted: 17 Jan 2011 (estimated)
Results: Posted 7 Jul 2016

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Treatment A first, then Treatment B, followed by Treatment C	Experimental	Drug: Cobimetinib, Drug: RabeprazoleTreatment 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	Experimental	Drug: Cobimetinib, Drug: RabeprazoleTreatment 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.

Who may qualify

Ages: 18 to 55 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (6 listed)

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

Key exclusion criteria (16 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
CobimetinibAlso: GDC-0973, XL518One 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.	Drug	Treatment A first, then Treatment B, followed by Treatment C, Treatment A first, then Treatment C, followed by Treatment B
RabeprazoleRabeprazole 20 mg will be administered orally once daily for 4 days starting on Day -4 and on Day 1 of the treatment period.	Drug	Treatment A first, then Treatment B, followed by Treatment C, Treatment A first, then Treatment C, followed by Treatment B

Primary outcome

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
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

Results and safety

Results posted to the registry on 7 Jul 2016, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Treatment A First, Then Treatment B, Followed by Treatment C	10	10
Treatment A First, Then Treatment C, Followed by Treatment B	10	10

Primary outcome: 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. Geometric mean (Geometric Coefficient of Variation). Unit: nanograms*hours/milliliter (ng*hr/mL)

Measure	Cobimetinib [Fasted] n = 20	Cobimetinib [Fasted] + Rabeprazole n = 16	Cobimetinib [Fed] + Rabeprazole n = 17
Value	778 (32.8)	864 (39.1)	846 (48.2)

Cobimetinib [Fasted] vs Cobimetinib [Fasted] + Rabeprazole: Ratio of Least Squares (LS) Means (in %): 111 (90% CI 98.02 to 124.99)
Cobimetinib [Fasted] + Rabeprazole vs Cobimetinib [Fed] + Rabeprazole: Ratio of LS Means (in %): 96.2 (90% CI 85.06 to 108.77)
Cobimetinib [Fasted] vs Cobimetinib [Fed] + Rabeprazole: Ratio of LS Means (in %): 106 (90% CI 94.53 to 119.91)

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

Primary outcome: 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. Geometric mean (Geometric Coefficient of Variation). Unit: nanograms per milliliter (ng/mL)

Measure	Cobimetinib [Fasted] n = 20	Cobimetinib [Fasted] + Rabeprazole n = 17	Cobimetinib [Fed] + Rabeprazole n = 17
Value	17.0 (35.3)	17.2 (36.0)	14.8 (51.2)

Cobimetinib [Fasted] vs Cobimetinib [Fasted] + Rabeprazole: Ratio of LS Means (in %): 100 (90% CI 85.09 to 118.03)
Cobimetinib [Fasted] + Rabeprazole vs Cobimetinib [Fed] + Rabeprazole: Ratio of LS Means (in %): 85.7 (90% CI 72.51 to 101.33)
Cobimetinib [Fasted] vs Cobimetinib [Fed] + Rabeprazole: Ratio of LS Means (in %): 85.9 (90% CI 72.94 to 101.17)

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

Adverse events

Time frame: Adverse events were recorded from start of study treatment in first period to end of last period (up to 36 days). Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Cobimetinib [Fasted]	0 of 20 (0%)	8 of 20 (40%)	Not reported
Cobimetinib [Fasted] + Rabeprazole	0 of 17 (0%)	10 of 17 (58.8%)	Not reported
Cobimetinib [Fed] + Rabeprazole	0 of 20 (0%)	9 of 20 (45%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 10 May 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Isabelle Rooney, M.D., PhD study director

Genentech, Inc.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Cobimetinib and Rabeprazole in people with Healthy Volunteer, run by Genentech, Inc..

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 May 2017. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Jul 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01277718.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 May 2017.