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

HCV Infection Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02397707
• Other study ID #: GS-US-338-1126
• Secondary ID: 2015-000342-30
• Status: Completed
• Phase: Phase 1
• Start date: March 24, 2015
• Est. completion date: March 4, 2016

Study information

• Verified date: April 2020
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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%).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: March 4, 2016
• Est. primary completion date: March 4, 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• HCV Infection
• Hepatitis C

Intervention

Drug:
• Voxilaprevir
100 mg tablet administered orally

Locations

Country	Name	City	State
Germany	APEX GmbH	München
New Zealand	Auckland Clinical Studies	Auckland
United States	Orlando Clinical Research Center	Orlando	Florida
United States	Texas Liver Institute	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Germany,  New Zealand, 

References & Publications (1)

Lawitz E, Marbury T, Kirby BJ, Au NT, Mathias A, Stamm LM, et al. The Effect of Renal or Hepatic Impairment on the Pharmacokinetics of GS-9857, A Pan-Genotypic HCV NS3/4A Protease Inhibitor [Abstract FRI-167]. J Hepatology 2016:S613-S4.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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