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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.
ClinicalTrials.gov Identifier:
NCT01249131
First received: November 24, 2010
Last updated: June 7, 2016
Last verified: June 2016
  Purpose
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.

Condition Intervention Phase
Healthy Volunteers
Drug: Cobimetinib
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-availability Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: A Phase I, Single-Dose, Randomized, Cross-Over, Relative Bioavailability, and Food Effect Study of GDC-0973 in Healthy Subjects

Resource links provided by NLM:


Further study details as provided by Genentech, Inc.:

Primary Outcome Measures:
  • Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) [ 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 ] [ Designated as safety issue: No ]
    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 Plasma Concentration (Cmax) [ 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 ] [ Designated as safety issue: No ]
  • Minimum Observed Plasma Concentration (Cmin) [ Time Frame: Day 1 at 0 hour (predose) ] [ Designated as safety issue: No ]
  • Apparent Oral Clearance (CL/F) [ 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 ] [ Designated as safety issue: No ]
    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.

  • Apparent Volume of Distribution (V/F) [ 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 ] [ Designated as safety issue: No ]
    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.


Enrollment: 20
Study Start Date: December 2010
Study Completion Date: January 2011
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment A first, then Treatment B, followed by Treatment C
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
Cobimetinib 20 mg will be given orally as tablet formulation in fasted or fed state, or as capsule formulation in fasted state.
Other Names:
  • GDC-0973
  • XL518
Experimental: Treatment A first, then Treatment C, followed by Treatment B
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
Cobimetinib 20 mg will be given orally as tablet formulation in fasted or fed state, or as capsule formulation in fasted state.
Other Names:
  • GDC-0973
  • XL518
Experimental: Treatment B first, then Treatment A, followed by Treatment C
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
Cobimetinib 20 mg will be given orally as tablet formulation in fasted or fed state, or as capsule formulation in fasted state.
Other Names:
  • GDC-0973
  • XL518
Experimental: Treatment B first, then Treatment C, followed by Treatment A
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
Cobimetinib 20 mg will be given orally as tablet formulation in fasted or fed state, or as capsule formulation in fasted state.
Other Names:
  • GDC-0973
  • XL518
Experimental: Treatment C first, then Treatment A, followed by Treatment B
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
Cobimetinib 20 mg will be given orally as tablet formulation in fasted or fed state, or as capsule formulation in fasted state.
Other Names:
  • GDC-0973
  • XL518
Experimental: Treatment C first, then Treatment B, followed by Treatment A
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
Cobimetinib 20 mg will be given orally as tablet formulation in fasted or fed state, or as capsule formulation in fasted state.
Other Names:
  • GDC-0973
  • XL518

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria

  • 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

Exclusion Criteria

  • Significant history or clinical manifestation of any significant metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, or psychiatric disorder
  • History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance
  • History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs except that appendectomy, hernia repair, and 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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01249131

Sponsors and Collaborators
Genentech, Inc.
Investigators
Study Director: Isabelle Rooney, M.D., PhD Genentech, Inc.
  More Information

Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT01249131     History of Changes
Other Study ID Numbers: MEK4953g 
Study First Received: November 24, 2010
Results First Received: June 7, 2016
Last Updated: June 7, 2016
Health Authority: United States: Food and Drug Administration

ClinicalTrials.gov processed this record on December 06, 2016