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

Phase 1

Completed

• Conditions: HCV Infection
• Interventions: Drug: Voxilaprevir

• Registration Number: NCT02397707
• Lead Sponsor: Gilead Sciences

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%).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2015-03-20
• Study First Submitted QC: 2015-03-20
• Study Start: 2015-03-24
• Study First Posted: 2015-03-25
• Primary Completion: 2016-03-04
• Study Completion: 2016-03-04
• Results First Submitted: 2020-03-04
• Results First Submitted QC: 2020-03-04
• Results First Posted: 2020-03-20
• Status Verified: 2020-04
• Last Update Submitted: 2020-04-02
• Last Update Posted: 2020-04-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 33

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Moderate Hepatic Impaired	Voxilaprevir	Participants with moderate hepatic impairment and matched healthy controls will receive a single dose of voxilaprevir on Day 1.
Severe Hepatic Impaired	Voxilaprevir	Participants with severe hepatic impairment and matched healthy controls will receive a single dose of voxilaprevir on Day 1.

Primary Outcome Measures

Name	Time	Method
Pharmacokinetic (PK) Parameter of Voxilaprevir: AUClast	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	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	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.

Trial Locations

Locations (4)

Orlando Clinical Research Center; 🇺🇸 Orlando, Florida, United States

Auckland Clinical Studies; 🇳🇿 Auckland, New Zealand

Texas Liver Institute; 🇺🇸 San Antonio, Texas, United States

APEX GmbH; 🇩🇪 München, Germany