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

Healthy Volunteer Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02300025
• Other study ID #: GP29342
• Status: Completed
• Phase: Phase 1
• First received: November 20, 2014
• Last updated: January 21, 2016
• Start date: August 2014
• Est. completion date: January 2015

Study information

• Verified date: January 2016
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: January 2015
• Est. primary completion date: January 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 74 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Healthy Volunteer

Intervention

Drug:
• cobimetinib
single oral 10-mg dose of cobimetinib

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Observed Plasma Concentration (Cmax)		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	No
Primary	Time to Reach Maximum Observed Plasma Concentration (Tmax)		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	No
Primary	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).	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	No
Primary	Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - 8)]	AUC (0 - 8) was defined as AUC from time zero (pre-dose) to extrapolated infinite time (0 - 8). It is obtained from AUC (0 - t) plus AUC (t- 8).	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	No
Primary	Extrapolated Area Under the Curve (AUC Percent [%] Extrapolated)	AUC% extrapolated was defined as the percentage of AUC [0-8] obtained by forward extrapolation. It is calculated as [AUC (0-8) minus AUC(0-t]*100/ AUC (0-8), where AUC [0-8] = Area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time (0-8) and AUC(0-t) is area under the plasma concentration time-curve from zero (pre-dose) to the last measured concentration.	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	No
Primary	Apparent Terminal Elimination Rate Constant (?Z)	?Z was defined as the magnitude of the slope of the linear regression of the log concentration versus time profile during the terminal phase.	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	No
Primary	Plasma Decay Half-Life (t1/2)	Plasma decay half-life is the time measured for the plasma concentration of cobimetinib to decrease by one half.	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	No
Primary	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. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.	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	No
Primary	Apparent Volume of Distribution (Vz/F)	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.	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	No