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

Genentech, Inc.28 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Masking

NONE

Enrollment

Conditions

Healthy Volunteer

Interventions

cobimetinibDRUG

single oral 10-mg dose of cobimetinib

Eligibility

Sex: ALLMin age: 18 YearsMax age: 74 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (3)

Unnamed facility

Anaheim, California, United States

Unnamed facility

Miami, Florida, United States

Unnamed facility

Orlando, Florida, United States

Outcomes

Primary Outcomes

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

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

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

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).

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

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

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- ∞).

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

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

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.

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

Apparent Terminal Elimination Rate Constant (λZ)

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

Data from ClinicalTrials.gov

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