Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of Velpatasvir in Participants With Chronic HCV Infection
- Registration Number
- NCT01740791
- Lead Sponsor
- Gilead Sciences
- Brief Summary
The primary objective of the study is to evaluate the safety, tolerability, and antiviral activity of velpatasvir (formerly GS-5816) in HCV treatment naive participants with genotypes 1-6.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 103
- HCV treatment-naive adult participants (18-65 years of age) with chronic HCV infection and plasma HCV RNA ≥ 5 log10 IU/mL at screening
- Agree to use protocol defined precautions against pregnancy
Key
- Chronic liver disease of a non-HCV etiology (e.g., hemochromatosis, Wilson's disease, α1 antitrypsin deficiency, cholangitis)
- Evidence of cirrhosis
- Evidence of current drug abuse
- Screening laboratory results outside the protocol specified requirements
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Velpatasvir 25 mg (GT 1a) Placebo Participants with GT 1a HCV infection will receive velpatasvir 25 mg or placebo once daily for 3 days under fasted conditions. Velpatasvir 150 mg (GT 3) Placebo Participants with GT 3 HCV infection will receive velpatasvir 150 mg or placebo once daily for 3 days under fasted conditions. Velpatasvir 100 mg (GT 1a) Placebo Participants with GT 1a HCV infection will receive velpatasvir 100 mg or placebo once daily for 3 days under fasted conditions. Velpatasvir 150 mg (GT 2) Placebo Participants with GT 2 HCV infection will receive velpatasvir 150 mg or placebo once daily for 3 days under fasted conditions. Velpatasvir 5 mg (GT 1a) Placebo Participants with genotype (GT) 1a HCV infection will receive velpatasvir 5 mg or placebo once daily for 3 days under fasted conditions. Velpatasvir 25 mg (GT 3) Placebo Participants with GT 3 HCV infection will receive velpatasvir 25 mg or placebo once daily for 3 days under fasted conditions. Velpatasvir 50 mg (GT 1a) Placebo Participants with GT 1a HCV infection will receive velpatasvir 50 mg or placebo once daily for 3 days under fasted conditions. Velpatasvir 150 mg (GT 1a) Placebo Participants with GT 1a HCV infection will receive velpatasvir 150 mg or placebo once daily for 3 days under fasted conditions. Velpatasvir 150 mg (GT 1b) Placebo Participants with GT 1b HCV infection will receive velpatasvir 150 mg or placebo once daily for 3 days under fasted conditions. Velpatasvir 50 mg (GT 3) Placebo Participants with GT 3 HCV infection will receive velpatasvir 50 mg or placebo once daily for 3 days under fasted conditions. Velpatasvir 150 mg (GT 4) Placebo Participants with GT 4 HCV infection will receive velpatasvir 150 mg or placebo once daily for 3 days under fasted conditions. Velpatasvir up to 400 mg (GT 2) Placebo Participants with GT 2 HCV infection will receive velpatasvir up to 400 mg or placebo once daily for 3 days under fasted conditions. Velpatasvir 5 mg (GT 1a) Velpatasvir Participants with genotype (GT) 1a HCV infection will receive velpatasvir 5 mg or placebo once daily for 3 days under fasted conditions. Velpatasvir 25 mg (GT 1a) Velpatasvir Participants with GT 1a HCV infection will receive velpatasvir 25 mg or placebo once daily for 3 days under fasted conditions. Velpatasvir 50 mg (GT 1a) Velpatasvir Participants with GT 1a HCV infection will receive velpatasvir 50 mg or placebo once daily for 3 days under fasted conditions. Velpatasvir 100 mg (GT 1a) Velpatasvir Participants with GT 1a HCV infection will receive velpatasvir 100 mg or placebo once daily for 3 days under fasted conditions. Velpatasvir 150 mg (GT 1a) Velpatasvir Participants with GT 1a HCV infection will receive velpatasvir 150 mg or placebo once daily for 3 days under fasted conditions. Velpatasvir 150 mg (GT 1b) Velpatasvir Participants with GT 1b HCV infection will receive velpatasvir 150 mg or placebo once daily for 3 days under fasted conditions. Velpatasvir 150 mg (GT 2) Velpatasvir Participants with GT 2 HCV infection will receive velpatasvir 150 mg or placebo once daily for 3 days under fasted conditions. Velpatasvir 25 mg (GT 3) Velpatasvir Participants with GT 3 HCV infection will receive velpatasvir 25 mg or placebo once daily for 3 days under fasted conditions. Velpatasvir 50 mg (GT 3) Velpatasvir Participants with GT 3 HCV infection will receive velpatasvir 50 mg or placebo once daily for 3 days under fasted conditions. Velpatasvir 150 mg (GT 3) Velpatasvir Participants with GT 3 HCV infection will receive velpatasvir 150 mg or placebo once daily for 3 days under fasted conditions. Velpatasvir 150 mg (GT 4) Velpatasvir Participants with GT 4 HCV infection will receive velpatasvir 150 mg or placebo once daily for 3 days under fasted conditions. Velpatasvir up to 400 mg (GT 2) Velpatasvir Participants with GT 2 HCV infection will receive velpatasvir up to 400 mg or placebo once daily for 3 days under fasted conditions.
- Primary Outcome Measures
Name Time Method Percentage of Participants Experiencing Treatment Emergent Adverse Events First dose date up to Day 17 + 2 (Day 19 if Day 17 visit missing) Treatment-emergent adverse events were defined as any new or worsening adverse event that began on or after the date of the first dose of study drug until the Day 17 study visit date + 2 (Day 19 if Day 17 visit missing).
Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities First dose date up to Day 17 + 2 (Day 19 if Day 17 visit missing) A treatment-emergent laboratory abnormality was defined as an increase of at least 1 abnormality grade from baseline at any postbaseline visit up to the Day 17 visit date + 2 days (or Day 19 if Day 17 visit was missing). The criteria used to grade laboratory results were as follows: Grade 1 (mild), Grade 2 (moderate), or Grade 3 (severe). Graded laboratory abnormalities were defined using the grading scheme defined in protocol (Gilead Sciences, Inc. Grading Scale for Severity of Adverse Events and Laboratory Abnormalities) for analysis purpose.
Antiviral Activity of Velpatasvir as Measured by Change in Plasma HCV RNA From Baseline Baseline; Days 4, 5, 6, 7, 8, 10, and 17 Participants who were genotyped incorrectly but received appropriate treatment for that genotype were included in that treatment group for the efficacy analysis. Data were summarized by treatment and placebo.
- Secondary Outcome Measures
Name Time Method Absolute HCV RNA Level Baseline; Days 4, 5, 6, 7, 8, 10, and 17 PK Parameter of Velpatasvir: AUCtau 0 (predose), 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, and 24 hours postdose at Day 3 AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
Pharmacokinetic (PK) Parameter of Velpatasvir: AUCinf 0 (predose), 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, and 24 hours postdose at Day 1 AUCinf is defined as the concentration of drug extrapolated to infinite time.
PK Parameter of Velpatasvir: Ctau 0 (predose), 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, and 24 hours postdose at Day 3 Ctau is defined as the observed drug concentration at the end of the dosing interval.
Number of Participants Who Have HCV RNA < Lower Limit of Quantitation (LLOQ) Detected Days 4, 5, 6, 7, and 8 The lower limit of quantitation (LLOQ) detection for HCV RNA levels was 25 IU/mL. HCV detected means calculated HCV RNA level is below LLOQ of the assay.
PK Parameter of Velpatasvir: Cmax 0 (predose), 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, and 24 hours postdose at Day 1 for single dose and Day 3 for multiple dose. Cmax is defined as the maximum observed plasma concentration of drug.
PK Parameter of Velpatasvir: CL/F 0 (predose), 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, and 24 hours postdose at Day 1 for single dose and Day 3 for multiple dose CL/F is defined as the apparent oral clearance following administration of the drug.
Number of Participants Achieving Reductions From Baseline in HCV RNA Baseline; Days 4, 5, 6, 7, 8, 10, and 17 Categorical declines from baseline were summarized by the number of participants with a \< 1, ≥ 1 to \< 2, ≥ 2 to \< 3, or ≥ 3 log10 IU/mL decrease in HCV RNA from baseline by treatment (velpatasvir dose/HCV genotype) and placebo at each collection time point through Day 17.
Plasma HCV RNA Levels by Treatment and IL28B Genotype Days 4, 5, 6, 7, 8, 10, and 17 Number of Participants With Nonstructural Protein 5A (NS5A) Resistance Associated Variants (RAVs) at Pretreatment or Postbaseline Timepoints First dose date up to Day 17 The full-length NS5A coding region was analyzed pretreatment (baseline) by deep sequencing using MiSeq for all 70 participants who received velpatasvir and for 8 of 17 participants who received placebo prior to and up to 2 weeks (Day 17) after dosing with velpatasvir. Participants were categorized by velpatasvir dose/HCV genotype and presence or absence of NS5A RAVs.
Trial Locations
- Locations (9)
West Coast Clinical Trials, LLC
🇺🇸Costa Mesa, California, United States
Avail Clinical Research, LLC
🇺🇸DeLand, Florida, United States
Orlando Clinical Research Center
🇺🇸Orlando, Florida, United States
Kansas City Gastroenterology and Hepatology
🇺🇸Kansas City, Missouri, United States
CRI Worldwide, LLC
🇺🇸Philadelphia, Pennsylvania, United States
New Orleans Center for Clinical Research-Knoxville
🇺🇸Knoxville, Tennessee, United States
Charles River Clinical Services Northwest, Inc.
🇺🇸Tacoma, Washington, United States
Alamo Medical Research
🇺🇸San Antonio, Texas, United States
Fundacion De Investigacion De Diego
🇵🇷San Juan, Puerto Rico