This is a Phase 2 Randomized, Double-Blind, Placebo-Controlled Study of GS-5885, GS-9451, Tegobuvir and Ribavirin; GS-5885, GS-9451 and Tegobuvir; GS-5885, GS-9451 and Ribavirin in Interferon Ineligible or Intolerant Subjects with Chronic Genotype 1a or 1b HCV Infection.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
163
GS-5885 tablet, 90 mg, QD
GS-9451 tablet, 200 mg QD
tegobuvir capsule, 30 mg BID
Safety and Tolerability
To evaluate safety and tolerability of combination therapy with GS-5885, GS-9451, tegobuvir and ribavirin or GS-5885, GS-9451 and tegobuvir or GS-5885, GS-9451 and ribavirin. Safety will be assessed during the study through the reporting of adverse events, clinical laboratory tests, physical examinations, vital signs and 12-lead ECGs at various time points during the study.
Time frame: Through 24 weeks of off-treatment follow-up
Antiviral Activity
To evaluate antiviral efficacy as measured by sustained virologic response (defined as HCV RNA \< lower limit of quantitation 24-weeks post-treatment) of combination therapy with GS-5885, GS-9451, tegobuvir and ribavirin or GS-5885, GS-9451 and tegobuvir or GS-5885, GS-9451 and ribavirin.
Time frame: Through 24 weeks of off-treatment follow-up
Viral Dynamics
To characterize the viral dynamics of GS-5885, GS-9451 and tegobuvir. The median change from baseline in HCV RNA and time-weighted average change from baseline through Day 10 will be assessed based on plasma HCV RNA sampling times to characterize the viral dynamics of GS-5885, GS-9451 and tegobuvir.
Time frame: Through 10 days of therapy
Composite (or Profile) of Pharmacokinetics
To characterize the steady state pharmacokinetics of GS-5885, GS-9451, tegobuvir and ribavirin (if appropriate). Cmax, Tmax, Clast, Tlast, Ctau, λz, AUCtau and T ½
Time frame: predose, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose
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ribavirin tablet (weight based: 1000 mg/day \<75 kg; 1200 mg/day ≥ 75 kg) divided twice daily (BID)
placebo matching ribavirin tablet, BID
placebo matching tegobuvir capsule, BID
California Liver Institute
Beverly Hills, California, United States
SCTI Research Foundation Liver Center
Coronado, California, United States
Scripps Clinic
La Jolla, California, United States
University of California, San Diego
La Jolla, California, United States
Kaiser Permanente Medical Center
Los Angeles, California, United States
Lightsource Medical
Los Angeles, California, United States
Medical Associates Research Group, Inc.
San Diego, California, United States
Kaiser Permanente
San Diego, California, United States
California Pacific Medical Center
San Francisco, California, United States
University of Colorado
Aurora, Colorado, United States
...and 40 more locations