A Study of Relative Bioavailability and Food Effect Study of Cobimetinib in Healthy Participants

NCT01249131 | Completed Phase 1 Results

• 1 other identifier: MEK4953g
• Study Type: interventional
• Target: 20
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study will be an open-label, randomized, 3-way, 6-sequence crossover study in healthy participants for determining the relative bioavailability of the tablet formulation to the capsule formulation and the effect of food on the relative bioavailability of the tablet formulation.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (5)

• Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf)

  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).

  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 Plasma Concentration (Cmax)

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

• Minimum Observed Plasma Concentration (Cmin)

  Day 1 at 0 hour (predose)

• Apparent Oral Clearance (CL/F)

  Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.

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

• Apparent Volume of Distribution (V/F)

  Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.

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

Study Arms (6)

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

EXPERIMENTAL

Treatment A: One 20-mg tablet of cobimetinib will be administered orally with 240 milliliter (mL) room temperature water after at least an 8-hour fast, in first intervention period. Treatment B: Four 5-mg capsules of cobimetinib will be administered orally with 240 mL room temperature water after at least an 8-hour fast, in second intervention period. Treatment C: One 20-mg tablet of cobimetinib will be administered orally with 240 mL room temperature water within 30 minutes of eating a standard Food and Drug Administration (FDA) high-fat meal, in third intervention period. The washout period between each period will be a minimum of 10 days.

Drug: Cobimetinib

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

EXPERIMENTAL

Treatment A: One 20-mg tablet of cobimetinib will be administered orally with 240 mL room temperature water after at least an 8-hour fast, in first intervention period. Treatment C: One 20-mg tablet of cobimetinib will be administered orally with 240 mL room temperature water within 30 minutes of eating a standard FDA high-fat meal, in second intervention period. Treatment B: Four 5-mg capsules of cobimetinib administered will be orally with 240 mL room temperature water after at least an 8-hour fast, in third intervention period.

Drug: Cobimetinib

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

EXPERIMENTAL

Treatment B: Four 5-mg capsules of cobimetinib will be administered orally with 240 mL room temperature water after at least an 8-hour fast, in first intervention period. Treatment A: One 20-mg tablet of cobimetinib will be administered orally with 240 mL room temperature water after at least an 8-hour fast, in second intervention period. Treatment C: One 20-mg tablet of cobimetinib will be administered orally with 240 mL room temperature water within 30 minutes of eating a standard FDA high-fat meal, in third intervention period.

Drug: Cobimetinib

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

EXPERIMENTAL

Treatment B: Four 5-mg capsules of cobimetinib will be administered orally with 240 mL room temperature water after at least an 8-hour fast, in first intervention period. Treatment C: One 20-mg tablet of cobimetinib will be administered orally with 240 mL room temperature water within 30 minutes of eating a standard FDA high-fat meal, in second intervention period. Treatment A: One 20-mg tablet of cobimetinib will be administered orally with 240 mL room temperature water after at least an 8-hour fast, in third intervention period.

Drug: Cobimetinib

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

EXPERIMENTAL

Treatment C: One 20-mg tablet of cobimetinib will be administered orally with 240 mL room temperature water within 30 minutes of eating a standard FDA high-fat meal, in first intervention period. Treatment A: One 20-mg tablet of cobimetinib will be administered orally with 240 mL room temperature water after at least an 8-hour fast, in second intervention period. Treatment B: Four 5-mg capsules of cobimetinib will be administered orally with 240 mL room temperature water after at least an 8-hour fast, in third intervention period.

Drug: Cobimetinib

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

EXPERIMENTAL

Treatment C: One 20-mg tablet of cobimetinib will be administered orally with 240 mL room temperature water within 30 minutes of eating a standard FDA high-fat meal, in first intervention period. Treatment B: Four 5-mg capsules of cobimetinib will be administered orally with 240 mL room temperature water after at least an 8-hour fast, in second intervention period. Treatment A: One 20-mg tablet of cobimetinib will be administered orally with 240 mL room temperature water after at least an 8-hour fast, in third intervention period.

Drug: Cobimetinib

Interventions

Cobimetinib DRUG

Cobimetinib 20 mg will be given orally as tablet formulation in fasted or fed state, or as capsule formulation in fasted state.

Also known as: GDC-0973, XL518

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

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Within body mass index range 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 and at each Check-in
• Negative hepatitis panel and anti-hepatitis C virus and negative human immunodeficiency virus (HIV) antibody screens
• Healthy males and females of non-child-bearing potential or who agree to use effective contraception

You may not qualify if:

• 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 cholecystectomy will be allowed
• History or presence of an abnormal ECG
• History of alcoholism or drug addiction prior to study start
• Use of any tobacco-containing or nicotine-containing products prior to study start
• Participation in any other investigational study drug trial in which receipt of an investigational study drug occurred within 28 days or 5 half-lives, whichever is longer, prior to study start
• Use of any prescription medications/products, including proton pump inhibitors, within 14 days prior to study start
• 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
• Predisposing factors to retinal vein occlusion (RVO)

Sponsors & Collaborators

• Genentech, Inc.: lead

MeSH Terms

Interventions

cobimetinib

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800-821-8590

Study Officials

• Isabelle Rooney, M.D., PhD

  Genentech, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 24, 2010
• First Posted: November 29, 2010
• Study Start: December 1, 2010
• Primary Completion: January 10, 2011
• Study Completion: January 10, 2011
• Last Updated: August 15, 2017
• Results First Posted: July 18, 2016

Record last verified: 2017-06