Safety, Tolerability, Pharmacokinetics and Antiviral Activity of GS-9669 in Subjects With Chronic Hepatitis C Virus Infection
- Conditions
- Hepatitis C
- Interventions
- Drug: GS-9669 tabletsDrug: Placebo to Match GS-9669 tablet
- Registration Number
- NCT01431898
- Lead Sponsor
- Gilead Sciences
- Brief Summary
This is a research study to evaluate the safety, tolerability and anti-viral activity of GS-9669 in patients with Hepatitis C infection.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 82
- Adult subjects 18-65 years of old, inclusive
- Documented chronic HCV infection to be of at least 6 months duration and plasma HCV RNA ≥ 5 log10 IU/mL at screening.
- HCV treatment naïve or PEG-IFN, IFN, and/or RBV experienced (treatment must have ceased at least 3 months prior to screening). Treatment experienced subjects should not exceed 40% of the subjects enrolled in each cohort
- Mono-infection with HCV genotype 1a for Cohorts 1, 2, 3, 4, and 5 and mono-infection with HCV genotype 1b for Cohort 6 and 7.
- Estimated creatinine clearance ≥ 70 mL/min,
- QTcF interval ≤ 450 msec for males and ≤ 470 msec for females, QRS duration < 120 msec, PR interval < 220 msec,
- Body mass index (BMI) of 19.0 to 34.0 kg/m^2, inclusive.
- Urine drug screen positive for illicit/illegal drugs
- ALT and AST levels > 5 times the upper limit of the normal range (ULN)
- Direct bilirubin > ULN, clinical or other laboratory evidence of hepatic decompensation (i.e., platelets < 90,000/mm^3, prothrombin time ≥ 1.5 × ULN and albumin < 3.5 g/dL) are not eligible for study participation.
- Subjects with an absolute neutrophil count (ANC) < 1,000 cells/mm^3 (< 750 cells/mm^3 for black or African-American subjects), hemoglobin (Hb) < 11 g/dL,
- Coinfected with hepatitis B virus (HBV), human immunodeficiency virus (HIV), or another HCV genotype other than genotype 1a/b are not eligible for study participation.
- Evidence of hepatocellular carcinoma (e.g., a-fetoprotein > 50 ng/mL or as indicated by recent ultrasound or other standard of care measure)
- History of significant cardiac disease. The following ECG abnormalities at screening are exclusionary: QTcF (QT corrected using Fridericia's formula=QT/RR^0.333) > 450 msec for males and > 470 for females; QRS > 120 msec (left or right hemiblock is not exclusionary); PR interval > 220 msec; bradycardia (< 45 beats per minute); second or third degree heart block.
- History of clinically-significant illness or any other major medical disorder that may interfere with subject treatment, assessment or compliance with the protocol
- History of a primary gastrointestinal disorder that could interfere with the absorption of the study drug or that could interfere with normal gastrointestinal anatomy or motility
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Multiple-dose, dose-escalation study of GS-9669 Placebo to Match GS-9669 tablet 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. Multiple-dose, dose-escalation study of GS-9669 GS-9669 tablets 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.
- Primary Outcome Measures
Name Time Method Safety and Tolerability 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 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.
- Secondary Outcome Measures
Name Time Method composite of Pharmacokinetics 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 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
Viral Dynamics and Pharmacodynamics 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.
Trial Locations
- Locations (9)
Avail Clinical Research, LLC
🇺🇸Deland, Florida, United States
Impact Clinical Trials
🇺🇸Las Vegas, Nevada, United States
University of Utah Health Sciences Center
🇺🇸Salt Lake City, Utah, United States
CRI Worldwide
🇺🇸Philadelphia, Pennsylvania, United States
Orlando Clinical Research Center
🇺🇸Orlando, Florida, United States
Lifetree Clinical Research, LC
🇺🇸Salt Lake City, Utah, United States
Fundacion de Investigacion de Diego
🇵🇷San Juan, Puerto Rico
Charles River Clinical Services Northwest
🇺🇸Tacoma, Washington, United States
Alamo Medical Research
🇺🇸San Antonio, Texas, United States