Study to Evaluate the Pharmacokinetics of Velpatasvir in Participants With Normal Renal Function and Severe Renal Impairment

A Phase 1, Open-Label, Parallel-Group, Single-Dose Study to Evaluate the Pharmacokinetics of GS-5816 in Subjects With Normal Renal Function and Severe Renal Impairment

The primary objective of the study is to evaluate the single-dose pharmacokinetics (PK) of velpatasvir (formerly GS-5816) in participants with severe renal impairment using matched healthy participants as a control group.

Study Overview

• Status: Completed
• Conditions: Hepatitis C Virus
• Intervention / Treatment: Drug: Velpatasvir

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 1

Contacts and Locations

Study Locations

• New Zealand
  • Christchurch, New Zealand, 08011
• United States
  • Florida
    • Miami, Florida, United States, 33014
    • Orlando, Florida, United States, 32809
  • Minnesota
    • Saint Paul, Minnesota, United States, 55114
  • Texas
    • San Antonio, Texas, United States, 78215

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• General good health with stable chronic kidney disease in Severe Renal Impairment Group
• Screening labs within defined thresholds
• Creatinine clearance must be < 30 mL/min for Severe Renal Impairment group, and ≥ 90 mL/min for Normal Renal Function group

Key Exclusion Criteria:

• Females who are pregnant or nursing, or males who have a pregnant partner
• Infection with hepatitis B virus (HBV), hepatitis C virus (HCV) or HIV
• History of clinically significant illness (including psychiatric or cardiac) or any other medical disorder that may interfere with participant treatment and/or adherence to the protocol

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: Participants with renal impairment; Participants with severe renal impairment will receive a single dose of velpatasvir.	Drug: Velpatasvir; Velpatasvir 100 mg (2 x 50 mg tablets) administered orally; Other Names: GS-5816
Active Comparator: Participants with normal renal function; Participants with normal renal function will receive a single dose of velpatasvir.	Drug: Velpatasvir; Velpatasvir 100 mg (2 x 50 mg tablets) administered orally; Other Names: GS-5816

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic (PK) Parameter of Velpatasvir: AUClast	AUClast is defined as the area under the plasma concentration versus time curve from time zero to the last quantifiable concentration.	Pre-dose (≤ 5 min), 0.5, 1, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 18, 24, 48, 72, 96, and 120 hours post-dose on Day 1
PK Parameter of Velpatasvir: AUCinf	AUCinf is defined as the area under the plasma concentration versus time curve extrapolated to infinite time.	Pre-dose (≤ 5 min), 0.5, 1, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 18, 24, 48, 72, 96, and 120 hours post-dose on Day 1
PK Parameter of Velpatasvir: Cmax	Cmax is defined as the maximum observed plasma concentration of drug.	Pre-dose (≤ 5 min), 0.5, 1, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 18, 24, 48, 72, 96, and 120 hours post-dose on Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Experiencing Treatment-Emergent Adverse Events	Treatment-emergent adverse events (TEAEs) were defined as any adverse events (AEs) with an onset date on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug.	First dose date plus 30 days
Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities	A treatment-emergent laboratory abnormality was defined as an increase of at least 1 abnormality grade from baseline and occurring after the first dose of study drug and within 30 days after last study drug administration. The severity of laboratory abnormalities was assessed as Grade 0, 1 (mild), 2 (moderate), 3 (severe), or 4 (potentially life threatening).	First dose date plus 30 days
Percentage Protein Binding of Velpatasvir	Mean velpatasvir protein binding (percentage free and percentage bound) was determined in all participants at 2 or 3 hours post-dose. Protein binding was assessed at Tmax whenever possible or at the time point closest to Tmax for each participant.	2 or 3 hours post-dose on Day 1

Collaborators and Investigators

• Sponsor: Gilead Sciences

Study record dates

Study Major Dates

• Study Start (Actual): December 16, 2013
• Primary Completion (Actual): June 9, 2014
• Study Completion (Actual): June 9, 2014

Study Registration Dates

• First Submitted: December 2, 2013
• First Submitted That Met QC Criteria: December 2, 2013
• First Posted (Estimate): December 6, 2013

Study Record Updates

• Last Update Posted (Actual): November 16, 2020
• Last Update Submitted That Met QC Criteria: October 20, 2020
• Last Verified: October 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; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Hepatitis; Hepatitis C; Anti-Infective Agents; Antiviral Agents; Velpatasvir
• Other Study ID Numbers: GS-US-281-1056; 2013-004113-41 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No