Phase 1
N=28
A Study to Evaluate the Pharmacokinetics and Safety of Cobimetinib in Volunteers With and Without Liver Damage
Healthy Volunteer
Bottom Line
View on ClinicalTrials.gov: NCT02300025 ↗Enrolled (actual)
28
Serious AEs
0.0%
Results posted
Feb 2016
Primary outcome: Primary: Maximum Observed Plasma Concentration (Cmax) — 10.7; 9.00; 8.03; 3.97 nanograms per milliliter (ng/mL)
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- cobimetinib (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Genentech, Inc.
- Primary completion
- Jan 2015
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Maximum Observed Plasma Concentration (Cmax) |
10.7; 9.00; 8.03; 3.97 | — |
| PRIMARY Time to Reach Maximum Observed Plasma Concentration (Tmax) |
2; 6; 4; 2 | — |
| PRIMARY Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] |
604; 498; 539; 268 | — |
| PRIMARY Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] |
637; 530; 579; 370 | — |
| PRIMARY Extrapolated Area Under the Curve (AUC Percent [%] Extrapolated) |
7.37; 6.69; 8.17; 15.90 | — |
| PRIMARY Apparent Terminal Elimination Rate Constant (λZ) |
0.00942; 0.00852; 0.00702; 0.00509 | — |
| PRIMARY Plasma Decay Half-Life (t1/2) |
79.1; 95.2; 104.0; 143.0 | — |
| PRIMARY Apparent Oral Clearance (CL/F) |
23.4; 22.9; 21.9; 31.7 | — |
| PRIMARY Apparent Volume of Distribution (Vz/F) |
2580; 2880; 3230; 6280 | — |
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
Data sourced from ClinicalTrials.gov (NCT02300025). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.