Pharmacokinetics of Voxilaprevir in Adults With Normal Renal Function and Severe Renal Impairment

A Phase 1 Open-Label, Parallel-Group, Single-Dose Study to Evaluate the Pharmacokinetics of GS-9857 in Subjects With Normal Renal Function and Severe Renal Impairment

The primary objective of this study is to evaluate the pharmacokinetics, safety, and tolerability of voxilaprevir (formerly GS-9857) in participants with severe renal impairment and matched healthy control participants.

Study Overview

• Status: Completed
• Conditions: HCV Infection
• Intervention / Treatment: Drug: Voxilaprevir

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • München, Germany, 81241
    • Apex Gmbh
• New Zealand
  • Christchurch, New Zealand, 8011
    • Christchurch Clinical Studies Trust Ltd
• United States
  • Florida
    • Orlando, Florida, United States, 32809
      • Orlando Clinical Research Center
  • Texas
    • San Antonio, Texas, United States, 78215
      • Texas Liver Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 severe renal impairment:

  • Stable chronic kidney disease
  • Creatinine clearance (CLcr) < 30 mL/min

Key Exclusion Criteria:

• All individuals:

  • Pregnant or nursing female or male with pregnant female partner
  • Hepatitis B virus, hepatitis C virus (HCV) or 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 severe renal impairment:

  • Anticipated to require dialysis within 90 days of study dosing

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Normal Renal Function; Participants will receive a single dose of voxilaprevir on Day 1.	Drug: Voxilaprevir; 100 mg tablet administered orally; Other Names: GS-9857
Experimental: Severe Renal Impairment; Participants will receive a single dose of voxilaprevir on Day 1.	Drug: Voxilaprevir; 100 mg tablet administered orally; Other Names: GS-9857

What is the study measuring?

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 (predose ≤ 5 min) and 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: 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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Experienced Treatment-Emergent Adverse Events (TEAE) and Laboratory Abnormalities	The percentage of participants experiencing any TEAE or treatment-emergent laboratory abnormality was summarized.	First dose date to Day 31

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Investigators: Study Director: Gilead Study Director, MD, PhD, Gilead Sciences

Publications and helpful links

General Publications

• Lawitz E, Marbury T, Kirby BJ, Au NT, Mathias A, Stamm LM, Wei H, Sajwani K, Klein G, Gane E, Robson R. The effect of renal or hepatic impairment on the pharmacokinetics of GS-9857, a pangenotypic HCV NS3/4A protease inhibitor. The International Liver Congress; 2016; Barcelona, Spain.

Study record dates

Study Major Dates

• Study Start (Actual): May 5, 2015
• Primary Completion (Actual): September 28, 2015
• Study Completion (Actual): September 28, 2015

Study Registration Dates

• First Submitted: March 25, 2015
• First Submitted That Met QC Criteria: March 25, 2015
• First Posted (Estimate): March 30, 2015

Study Record Updates

• Last Update Posted (Actual): March 20, 2020
• Last Update Submitted That Met QC Criteria: March 4, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Kidney Diseases; Urologic Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Hepatitis; Hepatitis C; Renal Insufficiency
• Other Study ID Numbers: GS-US-338-1125; 2015-000341-23 (EudraCT Number)