Participants with genotype 1 HCV infection were randomized to 1 of 3 sofosbuvir doses (100 mg, 200 mg, or 400 mg) or matching placebo once daily based upon stratification for IL28B status (CC or CT/TT). Placebo tablets were administered to participants receiving 100 mg active sofosbuvir (3 placebo tablets) and 200 mg active sofosbuvir (2 placebo tablets) in order to maintain the study blind. Participants received sofosbuvir/matching placebo from Day 0 to 27. Participants also received treatment with PEG+RBV starting on Day 0 of the study which continued for 48 weeks. Participants were evaluated for sustained virologic response (SVR) for an additional 24 weeks following completion of study treatment.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
64
Sofosbuvir tablet(s) administered orally once daily
Placebo to match sofosbuvir administered orally once daily
Pegylated interferon alfa-2a (PEG) 180 μg was administered once weekly by subcutaneous injection.
Ribavirin (RBV) tablets were administered orally in a divided daily dose according to package insert weight-based dosing recommendations (\< 75kg = 1000 mg and ≥ 75 kg = 1200 mg).
Quest Clinical Research
San Francisco, California, United States
University of Florida
Gainesville, Florida, United States
Orlando Immunology Center
Orlando, Florida, United States
Duke University
Durham, North Carolina, United States
Alamo Medical Research Center
San Antonio, Texas, United States
Virginia Mason Medical Center
Seattle, Washington, United States
Fundacion de Investigacion de Diego
Santurce, Puerto Rico, Puerto Rico
Percentage of Participants Who Experienced Adverse Events During the Sofosbuvir Treatment Period
Adverse events (AEs) occurring during the sofosbuvir treatment period were summarized across the participant population. A participant was counted once if they had a qualifying event.
Time frame: Baseline to Week 4
Change in Circulating HCV RNA at Week 4
Time frame: Baseline to Week 4
Percentage of Participants With Rapid Virologic Response at Week 4
Rapid virologic response (RVR) was defined as HCV RNA below the limit of detection (LOD \[15 IU/mL\]) at Week 4.
Time frame: Week 4
Percentage of Participants With Sustained Virologic Response (SVR) at 12 and 24 Weeks After Last Dose of PEG+RBV Following Completion of 48 Weeks of Treatment
SVR at 12 weeks (SVR12) and 24 weeks (SVR24) was defined as HCV RNA \< LOD 12 and 24 weeks after last dose of PEG+RBV, respectively, following completion of 48 weeks of treatment (4 weeks of sofosbuvir or matching placebo and PEG+RBV, followed by an additional 44 weeks of PEG+RBV).
Time frame: Post-treatment Weeks 12 and 24
Plasma Pharmacokinetics of Sofosbuvir: Cmax at Day 0
The Cmax of sofosbuvir was measured at Day 0 following a single dose of sofosbuvir. Cmax is defined as the maximum concentration of drug.
Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose
Plasma Pharmacokinetics of Sofosbuvir: Cmax at Day 27
The Cmax of sofosbuvir was measured at Day 27 following continuous dosing of sofosbuvir.
Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose)
Plasma Pharmacokinetics of Sofosbuvir: AUCinf at Day 0
The AUCinf of sofosbuvir was analyzed at Day 0 (following a single dose of sofosbuvir). AUCinf is defined as the concentration of drug (area under the plasma concentration versus time curve) extrapolated to infinite time.
Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose
Plasma Pharmacokinetics of Sofosbuvir: AUCtau at Day 27
The AUCtau of sofosbuvir was analyzed at Day 27 (following continuous dosing of sofosbuvir). AUCtau is defined as the concentration of drug (area under the plasma concentration versus time curve) over the dosing interval.
Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose)
Plasma Pharmacokinetics of GS-331007: Cmax at Day 0
The Cmax of GS-331007 was measured at Day 0 following a single dose of sofosbuvir. GS-331007 is the predominant circulating metabolite of sofosbuvir.
Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose
Plasma Pharmacokinetics of GS-331007: Cmax at Day 27
The Cmax of GS-331007 was measured at Day 27 following continuous dosing of sofosbuvir.
Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose)
Plasma Pharmacokinetics of GS-331007: AUCinf at Day 0
The AUCinf of GS-331007 was analyzed at Day 0 (following a single dose of sofosbuvir).
Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose
Plasma Pharmacokinetics of GS-331007: AUCtau at Day 27
The AUCtau of GS-331007 was analyzed at Day 27 (following continuous dosing of sofosbuvir).
Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose)
Plasma Pharmacokinetics of GS-566500: Cmax at Day 0
The Cmax of GS-566500 was measured at Day 0 following a single dose of sofosbuvir. GS-566500 is one of the major metabolites of sofosbuvir.
Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose
Plasma Pharmacokinetics of GS-566500: Cmax at Day 27
The Cmax of GS-566500 was measured at Day 27 following continuous dosing of sofosbuvir.
Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose)
Plasma Pharmacokinetics of GS-566500: AUCinf at Day 0
The AUCinf of GS-566500 was analyzed at Day 0 (following a single dose of sofosbuvir).
Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose
Plasma Pharmacokinetics of GS-566500: AUCtau at Day 27
The AUCtau of GS-566500 was analyzed at Day 27 (following continuous dosing of sofosbuvir).
Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose)
Percentage of Participants Who Developed Resistance to Sofosbuvir
Time frame: Baseline to Week 4
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.