Safety, Tolerability, Pharmacokinetics and Antiviral Activity of GS-9669 in Subjects With Chronic Hepatitis C Virus Infection

Hepatitis C Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01431898
• Other study ID #: GS-US-257-0102
• Status: Completed
• Phase: Phase 1
• First received: September 1, 2011
• Last updated: July 23, 2012
• Start date: September 2011
• Est. completion date: May 2012

Study information

• Verified date: March 2012
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This is a research study to evaluate the safety, tolerability and anti-viral activity of GS-9669 in patients with Hepatitis C infection.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 82
• Est. completion date: May 2012
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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

Masking: Single Blind (Subject), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C, Chronic
• Hepatitis, Chronic
• Virus Diseases

Intervention

Drug:
• GS-9669 tablets

• Placebo to Match GS-9669 tablet

Locations

Country	Name	City	State
Puerto Rico	Fundacion de Investigacion de Diego	San Juan
United States	Avail Clinical Research, LLC	Deland	Florida
United States	Impact Clinical Trials	Las Vegas	Nevada
United States	Impact Clinical Trials	Los Angeles	California
United States	Orlando Clinical Research Center	Orlando	Florida
United States	CRI Worldwide	Philadelphia	Pennsylvania
United States	Lifetree Clinical Research, LC	Salt Lake City	Utah
United States	University of Utah Health Sciences Center	Salt Lake City	Utah
United States	Alamo Medical Research	San Antonio	Texas
United States	Charles River Clinical Services Northwest	Tacoma	Washington
United States	CRI Worldwide	Willingboro	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and Tolerability	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.	through 24 weeks of off-treatment follow-up
Primary	Antiviral Activity	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.	through 24 weeks of off-treatment follow-up
Secondary	Viral Dynamics and Pharmacodynamics	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.	Through 17 days of therapy
Secondary	composite of Pharmacokinetics	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, ?z, AUC0-last, AUCtau, , CL/F, and T½.	Through 17 days of therapy
Secondary	Genotypic Changes	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	through 24 weeks of off-treatment follow-up