Clinical trial NCT02397707: Pharmacokinetics of Voxilaprevir in Adults With Normal Hepatic Function and Moderate or Severe Hepatic Impairment
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HCV Infection
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2015-03-25
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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%).


Eligibility criteria: 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.

Primary outcomes:
measure: Pharmacokinetic (PK) Parameter of Voxilaprevir: AUClast
timeFrame: 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
measure: PK Parameter of Voxilaprevir: AUCinf
timeFrame: 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
measure: PK Parameter of Voxilaprevir: Cmax
timeFrame: 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
Secondary outcomes:
Other outcomes:
Locations:
city: Orlando
country: United States
facility: Orlando Clinical Research Center
state: Florida
city: San Antonio
country: United States
facility: Texas Liver Institute
state: Texas
city: München
country: Germany
facility: APEX GmbH
city: Auckland
country: New Zealand
facility: Auckland Clinical Studies
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
citation: 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.