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

NCT02300025 | Completed Phase 1 Results

• 1 other identifier: GP29342
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 3

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.

Conditions

Healthy Volunteer

Outcome Measures

Primary Outcomes (9)

• 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

• 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

• 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

• 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- ∞).

  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.

  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.

  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 (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

• 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

• 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

Study Arms (4)

Cohort 1: Normal function

EXPERIMENTAL

Drug: cobimetinib

Cohort 2: Mild Hepatic Impairment

EXPERIMENTAL

Drug: cobimetinib

Cohort 3: Moderate Hepatic Impairment

EXPERIMENTAL

Drug: cobimetinib

Cohort 4: Severe Hepatic Impairment

EXPERIMENTAL

Drug: cobimetinib

Interventions

cobimetinib DRUG

single oral 10-mg dose of cobimetinib

Cohort 1: Normal function; Cohort 2: Mild Hepatic Impairment; Cohort 3: Moderate Hepatic Impairment; Cohort 4: Severe Hepatic Impairment

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (3)

Unknown Facility

Anaheim, California, 92801, United States

Location

Unknown Facility

Miami, Florida, 330014, United States

Location

Unknown Facility

Orlando, Florida, 32809, United States

Location

MeSH Terms

Interventions

cobimetinib

Results Point of Contact

• Title: Medical Communications
• Organization: Genentech

genentech@druginfo.com

800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 20, 2014
• First Posted: November 24, 2014
• Study Start: August 1, 2014
• Primary Completion: January 1, 2015
• Study Completion: January 1, 2015
• Last Updated: February 19, 2016
• Results First Posted: February 19, 2016

Record last verified: 2016-01

Locations

US (3)