Safety, Tolerability, Pharmacokinetics and Antiviral Activity of GS-9669 in Subjects With Chronic Hepatitis C Virus Infection
|Hepatitis C||Drug: GS-9669 tablets Drug: Placebo to Match GS-9669 tablet||Phase 1|
|Study Design:||Masking: Single Blind (Participant)
Primary Purpose: Treatment
|Official Title:||A Phase 1b, Randomized, Single-Blind, Multiple-Dose Ranging Study Evaluating the Safety, Tolerability, Pharmacokinetics and Antiviral Activity of GS-9669 in Subjects With Chronic Hepatitis C Virus Infection|
- Safety and Tolerability [ Time Frame: through 24 weeks of off-treatment follow-up ]
To evaluate safety and tolerability of escalating multiple oral doses of GS 9669.
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.
- Antiviral Activity [ Time Frame: through 24 weeks of off-treatment follow-up ]To evaluate antiviral activity of GS-9669 against HCV in genotype-1a and 1b (GT1a/b) subjects. This will be evaluated using change from baseline in plasma HCV RNA. Reduction in HCV RNA will be summarized as categorical (as < 1, ≥ 1 to <2, ≥ 2 to <3, or ≥ 3 log10 IU/mL) reduction from baseline.
- Viral Dynamics and Pharmacodynamics [ Time Frame: Through 17 days of therapy ]To characterize the viral dynamics of GS-9669. The median change from baseline in HCV RNA and time-weighted average change from baseline through Day 3 will be assessed based on plasma HCV RNA sampling times to characterize the viral dynamics of GS-9669.
- composite of Pharmacokinetics [ Time Frame: Through 17 days of therapy ]To characterize the plasma PK parameters of GS-9669. The secondary PK endpoints will be evaluated using standard non-compartmental methods. Relevant PK parameters will be determined using standard non-compartmental methods with the linear-logarithmic trapezoidal rule utilizing a PK data analysis program (e.g., WinNonlin®) for GS-9669 as appropriate: Cmax, Tmax, Clast, Tlast, Ctau, λz, AUC0-last, AUCtau, , CL/F, and T½.
- Genotypic Changes [ Time Frame: through 24 weeks of off-treatment follow-up ]To characterize genotypic changes from baseline in the NS5B coding region of HCV following multiple dose administration of GS-9669 and for up to 24 weeks thereafter
|Study Start Date:||September 2011|
|Study Completion Date:||May 2012|
|Primary Completion Date:||December 2011 (Final data collection date for primary outcome measure)|
Experimental: Multiple-dose, dose-escalation study of GS-9669
Multiple-dose, dose-escalation study of GS-9669, a nonnucleotide NS5B inhibitor of hepatitis C virus (HCV), in subjects with chronic HCV infection. Dosing is planned in up to 7 unique dosing cohorts. Each cohort will be comprised of 10 genotype 1a (Cohorts 1, 2, 3, 4, and 5) or genotype 1b (Cohort 6 and 7), with eight subjects randomized to receive active drug and two subjects randomized to receive placebo per cohort.
Drug: GS-9669 tablets
Other Names:Drug: Placebo to Match GS-9669 tablet
Please refer to this study by its ClinicalTrials.gov identifier: NCT01431898
|United States, California|
|Impact Clinical Trials|
|Los Angeles, California, United States, 90036|
|United States, Florida|
|Avail Clinical Research, LLC|
|Deland, Florida, United States, 32720|
|Orlando Clinical Research Center|
|Orlando, Florida, United States, 32809|
|United States, Nevada|
|Impact Clinical Trials|
|Las Vegas, Nevada, United States, 89106|
|United States, New Jersey|
|Willingboro, New Jersey, United States, 08046|
|United States, Pennsylvania|
|Philadelphia, Pennsylvania, United States, 19139|
|United States, Texas|
|Alamo Medical Research|
|San Antonio, Texas, United States, 78215|
|United States, Utah|
|Lifetree Clinical Research, LC|
|Salt Lake City, Utah, United States, 84106|
|University of Utah Health Sciences Center|
|Salt Lake City, Utah, United States, 84132|
|United States, Washington|
|Charles River Clinical Services Northwest|
|Tacoma, Washington, United States, 98418|
|Fundacion de Investigacion de Diego|
|San Juan, Puerto Rico, 00927|
|Study Director:||Stephen Rossi, PharmD||Gilead Sciences|