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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Hepatitis C Virus

Intervention / Treatment
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* Drug: Velpatasvir


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 79 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Participants with renal impairment<br>Participants with severe renal impairment will receive a single dose of velpatasvir. | Drug: Velpatasvir<br>* Velpatasvir 100 mg (2 x 50 mg tablets) administered orally<br>* Other names: GS-5816;|
| Active Comparator: Participants with normal renal function<br>Participants with normal renal function will receive a single dose of velpatasvir. | Drug: Velpatasvir<br>* Velpatasvir 100 mg (2 x 50 mg tablets) administered orally<br>* Other names: GS-5816;|

What is the study measuring?
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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 |