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Completed

NCT Number: NCT02300025

A Study to Evaluate the Pharmacokinetics and Safety of Cobimetinib in Volunteers With and Without Liver Damage

This study is an open-label, multi-center, single-dose, parallel group study to determine the pharmacokinetics, safety, and tolerability of cobimetinib administered at 10 mg to fasted male and female adult subjects with varying degrees of hepatic function. The study will be conducted based on the Child-Pugh classification of hepatic impairment. The anticipated duration of the study is 7.5 weeks. The target sample sizes are: 18 volunteers with varying degrees of hepatic function and up to 12 healthy control volunteers.

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Key information

Conditions

Healthy Volunteer

Age range

18 year–74 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Anaheim, California, United States

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Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Male and female subjects between 18 and 74 years of age, inclusive
  • Body weight >/=45 kg and body mass index between 17 and 41 kg/m2, inclusive
  • Subjects with hepatic impairment must have a Child-Pugh score of 5 to 6 (mild), 7 to 9 (moderate), or 10 to 15 (severe) and have stable hepatic insufficiency within 1 month prior to Screening and a stable medication regimen for at least 1 month prior to Check-in
  • Agreement to use highly effective contraceptive methods as defined in the protocol

Exclusion criteria

  • Significant illness, including infections, or hospitalization within the 2 weeks prior to dosing, except for subjects with hepatic impairment who due to their liver disease may be affected by significant medical problems which require frequent hospitalizations. Invasive systemic fungal infections need to be fully treated prior to study entry
  • Significant history or clinical manifestations of any cardiac event that would put the subject at risk in the opinion of the Investigator
  • Use of drugs of abuse within 1 month of Screening or during the entire study
  • Any acute or chronic condition that, in the opinion of the Investigator, would limit the subject's ability to complete and/or participate in this clinical study

Treatment and study plan

Cobimetinib

Drug

single oral 10-mg dose of cobimetinib

Primary outcomes

  1. Maximum Observed Plasma Concentration (Cmax)

    Time frame: Pre-dose (0 hours [hrs]), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 264, 336, 456, and 576 hrs post-dose

  2. Time to Reach Maximum Observed Plasma Concentration (Tmax)

    Time frame: Pre-dose (0 hrs), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 264, 336, 456, and 576 hrs post-dose

  3. Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)]

    Time frame: Pre-dose (0 hrs), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 264, 336, 456, and 576 hrs post-dose

    AUC (0-t) was defined as area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-t).

  4. Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)]

    Time frame: Pre-dose (0 hrs), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 264, 336, 456, and 576 hrs post-dose

    AUC (0 - ∞) was defined as AUC from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t- ∞).

  5. Extrapolated Area Under the Curve (AUC Percent [%] Extrapolated)

    Time frame: Pre-dose (0 hrs), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 264, 336, 456, and 576 hrs post-dose

    AUC% extrapolated was defined as the percentage of AUC [0-∞] obtained by forward extrapolation. It is calculated as [AUC (0-∞) minus AUC(0-t]*100/ AUC (0-∞), where AUC [0-∞] = Area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time (0-∞) and AUC(0-t) is area under the plasma concentration time-curve from zero (pre-dose) to the last measured concentration.

  6. Apparent Terminal Elimination Rate Constant (λZ)

    Time frame: Pre-dose (0 hrs), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 264, 336, 456, and 576 hrs post-dose

    λZ was defined as the magnitude of the slope of the linear regression of the log concentration versus time profile during the terminal phase.

  7. Plasma Decay Half-Life (t1/2)

    Time frame: Pre-dose (0 hrs), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 264, 336, 456, and 576 hrs post-dose

    Plasma decay half-life is the time measured for the plasma concentration of cobimetinib to decrease by one half.

  8. Apparent Oral Clearance (CL/F)

    Time frame: Pre-dose (0 hrs), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 264, 336, 456, and 576 hrs post-dose

    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. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.

  9. Apparent Volume of Distribution (Vz/F)

    Time frame: Pre-dose (0 hrs), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 264, 336, 456, and 576 hrs post-dose

    Volume of distribution was 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. Vz/F after the oral dose is influenced by the fraction absorbed.

Sponsors and collaborators

Lead sponsor

Genentech, Inc.

Industry

Registry information

Important dates

Study start
2014
Primary completion
2015
Study completion
2015
First posted
Nov 24, 2014
Registry last updated
Feb 19, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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