Pharmacokinetics of Voxilaprevir in Adults With Normal Hepatic Function and Moderate or Severe Hepatic Impairment

Study Overview
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Brief Summary
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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%).

Official Title
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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

Conditions
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HCV Infection

Intervention / Treatment
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* Drug: Voxilaprevir


Participation Criteria
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Eligibility Criteria
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Key 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: Hepatitis C Virus (HCV) antibody and hepatitis B surface antigen negative Key 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 Spontaneous bacterial peritonitis currently or within the last 6 months Hospitalization within the last 2 months related to cirrhosis Confirmed hypotension Suspicion of hepatocellular carcinoma Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Moderate Hepatic Impaired<br>Participants with moderate hepatic impairment and matched healthy controls will receive a single dose of voxilaprevir on Day 1. | Drug: Voxilaprevir<br>* 100 mg tablet administered orally<br>* Other names: GS-9857;|
| Experimental: Severe Hepatic Impaired<br>Participants with severe hepatic impairment and matched healthy controls will receive a single dose of voxilaprevir on Day 1. | Drug: Voxilaprevir<br>* 100 mg tablet administered orally<br>* Other names: GS-9857;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic (PK) Parameter of Voxilaprevir: AUClast | 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. | 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 | 
| PK Parameter of Voxilaprevir: AUCinf | 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. | 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 | 
| PK Parameter of Voxilaprevir: Cmax | Cmax is defined as the maximum observed plasma concentration of drug.Data presented are unadjusted geometric means and confidence intervals. | 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 |