Clinical trial NCT02300025: A Study to Evaluate the Pharmacokinetics and Safety of Cobimetinib in Volunteers With and Without Liver Damage
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteer
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2014-11-24
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax)
timeFrame: 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
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax)
timeFrame: 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
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)]
timeFrame: 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
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)]
timeFrame: 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
measure: Extrapolated Area Under the Curve (AUC Percent [%] Extrapolated)
timeFrame: 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
measure: Apparent Terminal Elimination Rate Constant (λZ)
timeFrame: 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
measure: Plasma Decay Half-Life (t1/2)
timeFrame: 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
measure: Apparent Oral Clearance (CL/F)
timeFrame: 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
measure: Apparent Volume of Distribution (Vz/F)
timeFrame: 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
Secondary outcomes:
Other outcomes:
Locations:
city: Anaheim
country: United States
state: California
city: Miami
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: