A Phase 1 Open-Label, Parallel-Group, Single-Dose Study to Evaluate the Pharmacokinetics of GS-9857 in Subjects With Normal Hepatic Function and Moderate or Severe Hepatic Impairment
Overview
- Phase
- Phase 1
- Intervention
- Voxilaprevir
- Conditions
- HCV Infection
- Sponsor
- Gilead Sciences
- Enrollment
- 33
- Locations
- 4
- Primary Endpoint
- Pharmacokinetic (PK) Parameter of Voxilaprevir: AUClast
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
The primary objective of this study is to evaluate the pharmacokinetics (PK), safety, and tolerability of a single dose of voxilaprevir (formerly GS-9857) in participants with normal hepatic function, moderate hepatic impairment and severe hepatic impairment. Participants in the healthy control group will be matched to participants with impaired hepatic function by gender, age (± 10 years), and body mass index (± 15%).
Investigators
Eligibility Criteria
Inclusion Criteria
- •All individuals:
- •Screening laboratory values within defined thresholds for group
- •Use of two effective contraception methods if female of childbearing potential or sexually active male
- •For individuals with moderate hepatic impairment:
- •Diagnosis of chronic (\> 6 months) hepatic impairment
- •Score on the Child-Pugh-Turcotte (CPT) scale of 7-9 at screening (Child Pugh Class B).
- •For individuals with severe hepatic impairment:
- •Diagnosis of chronic (\> 6 months) hepatic impairment
- •Score on the CPT scale of 10-15 at screening (Child Pugh Class C)
- •For individuals with normal hepatic function:
Exclusion Criteria
- •All individuals:
- •Pregnant or nursing female or male with pregnant female partner
- •HIV infection
- •History of clinically significant illness or any other medical disorder that may interfere with the individual's treatment, assessment or compliance with the protocol
- •For individuals with moderate or severe hepatic impairment:
- •Active HCV infection
- •Current hepatic encephalopathy
- •Variceal bleeding in the last 6 months unless banded
- •Prior placement of a portosystemic shunt
- •History of hepatorenal or hepatopulmonary syndrome
Arms & Interventions
Moderate Hepatic Impaired
Participants with moderate hepatic impairment and matched healthy controls will receive a single dose of voxilaprevir on Day 1.
Intervention: Voxilaprevir
Severe Hepatic Impaired
Participants with severe hepatic impairment and matched healthy controls will receive a single dose of voxilaprevir on Day 1.
Intervention: Voxilaprevir
Outcomes
Primary Outcomes
Pharmacokinetic (PK) Parameter of Voxilaprevir: AUClast
Time Frame: 0 (pre-dose ≤ 5 minutes), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 48, 72, 96, and 120 hours post-dose
AUClast is defined as the area under the plasma concentration versus time curve from time zero to the last quantifiable concentration. Data presented are unadjusted geometric means and confidence intervals.
PK Parameter of Voxilaprevir: AUCinf
Time Frame: 0 (pre-dose ≤ 5 minutes), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 48, 72, 96, and 120 hours postdose
AUCinf is defined as the area under the plasma concentration versus time curve extrapolated to infinite time. Data presented are unadjusted geometric means and confidence intervals.
PK Parameter of Voxilaprevir: Cmax
Time Frame: 0 (pre-dose ≤ 5 minutes), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 48, 72, 96, and 120 hours postdose
Cmax is defined as the maximum observed plasma concentration of drug.Data presented are unadjusted geometric means and confidence intervals.