A Study Evaluating the Safety, Tolerability, Pharmacokinetics and Antiviral Activity of GS-6620 in Treatment Naïve Subjects With Chronic Hepatitis C Virus Infection

A Phase 1 Double-Blind, Randomized, Placebo-Controlled, Multiple Dose Ranging Study Evaluating the Safety, Tolerability, Pharmacokinetics and Antiviral Activity of GS-6620 in Treatment Naïve Subjects With Chronic Hepatitis C Virus Infection

A Double-Blind, Randomized, Placebo-Controlled, Multiple Dose Ranging Study Evaluating the Safety, Tolerability, Pharmacokinetics and Antiviral Activity of GS-6620 in Treatment Naïve Subjects with Chronic Hepatitis C Virus Infection.

Study Overview

• Status: Completed
• Conditions: Hepatitis C, Chronic
• Intervention / Treatment: Drug: GS-6620; Drug: GS-6620; Drug: GS-6620; Drug: GS-6620; Drug: GS-6620; Drug: GS-6620; Drug: GS-6620 tablet, 450 mg BID; Drug: GS-6620 tablet; Drug: GS-6620 tablet

• Study Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Phase 1

Contacts and Locations

Study Locations

• Puerto Rico
  • Puerto Rico, Puerto Rico, 00927
    • Fundación De Investigación De Diego
• United States
  • California
    • Anaheim, California, United States, 92801
      • Advanced Clinical Research Institute
    • Los Angeles, California, United States, 90057
      • Axis Clinical Trials
  • Florida
    • Deland, Florida, United States, 32720
      • Avail Clinical Research, LLC
    • Gainesville, Florida, United States, 32608
      • University of Florida - Gainesville
    • Orlando, Florida, United States, 32809
      • Orlando Clinical Research Center
    • Orlando, Florida, United States, 32803
      • Orlando Immunology Center
  • Missouri
    • St. Louis, Missouri, United States, 63104
      • Saint Louis University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19139
      • CRI Worldwide
  • Texas
    • Houston, Texas, United States, 77030
      • St. Luke Episcopal Hospital
    • San Antonio, Texas, United States, 78215
      • Alamo Medical Research
  • Utah
    • Salt Lake City, Utah, United States, 84106
      • Lifetree Clinical Research, LC
  • Washington
    • Tacoma, Washington, United States, 98418
      • Charles River Clinical Services Northwest

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult subjects (18-60 years of age or up to 64 years of age with approval)
• 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
• Estimated creatinine clearance ≥ 80 mL/min,
• QTcF interval ≤ 450 msec, QRS duration < 100 msec, PR interval < 220 msec,
• Body mass index (BMI) of 19.0 to 34.0 kg/m2, inclusive.
• Eligible subjects must also be HCV treatment-naïve.

Exclusion Criteria:

• Subjects with prior documentation of cirrhosis, excessive current alcohol intake, any evidence of hepatocellular carcinoma (i.e., α-fetoprotein > 50 ng/mL or by any other standard of care measure)
• 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 < 100,000/mm3, 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/mm3 (< 750 cells/mm3 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 type 1 for Cohorts 1-5 and type 2 or 3 for Cohort 6) are not eligible for study participation.
• Evidence of hepatocellular carcinoma
• Any sign of decompensated liver disease, including prothrombin time ≥ 1.5 X ULN, platelets < 100,000/mm3 or albumin < 3.5 g/dL at screening OR current or prior history of clinical hepatic decompensation (e.g., ascites, jaundice, encephalopathy or variceal hemorrhage)
• 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 Plan

How is the study designed?

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Cohort 1; (N = 10, genotype 1): (Active drug: 8, Matching Placebo: 2) 50 mg GS-6620 or placebo QD in the morning with food [total daily dose (TDD) = 50 mg] for 5 days	Drug: GS-6620; GS-6620 tablet, 50 mg QD; Drug: GS-6620; GS-6620 tablet, 100 mg QD; Drug: GS-6620; GS-6620 tablet, 300 mg QD; Drug: GS-6620; GS-6620 tablet, 100 mg QD, Fasted; Drug: GS-6620; GS-6620 tablet, 300 mg QD, Fasted; Drug: GS-6620; GS-6620 tablet, 900 mg QD, Fasted
Other: Cohort 2; (N = 10, genotype 1): (Active drug: 8, Matching Placebo: 2) 100 mg GS-6620 or placebo QD in the morning with food (TDD = 100 mg) for 5 days	Drug: GS-6620; GS-6620 tablet, 50 mg QD; Drug: GS-6620; GS-6620 tablet, 100 mg QD; Drug: GS-6620; GS-6620 tablet, 300 mg QD; Drug: GS-6620; GS-6620 tablet, 100 mg QD, Fasted; Drug: GS-6620; GS-6620 tablet, 300 mg QD, Fasted; Drug: GS-6620; GS-6620 tablet, 900 mg QD, Fasted
Other: Cohort 3; Cohort 3 (N = 10, genotype 1): (Active drug: 8, Matching Placebo: 2) 300 mg GS 6620 or placebo QD in the morning with food (TDD = 300 mg) for 5 days	Drug: GS-6620; GS-6620 tablet, 50 mg QD; Drug: GS-6620; GS-6620 tablet, 100 mg QD; Drug: GS-6620; GS-6620 tablet, 300 mg QD; Drug: GS-6620; GS-6620 tablet, 100 mg QD, Fasted; Drug: GS-6620; GS-6620 tablet, 300 mg QD, Fasted; Drug: GS-6620; GS-6620 tablet, 900 mg QD, Fasted
Other: Cohort 4; Cohort 4 (N = 10, genotype 1): (Active drug: 8, Matching Placebo: 2) 100 mg GS 6620 or placebo QD in the morning without food (TDD = 100 mg) for 5 days	Drug: GS-6620; GS-6620 tablet, 50 mg QD; Drug: GS-6620; GS-6620 tablet, 100 mg QD; Drug: GS-6620; GS-6620 tablet, 300 mg QD; Drug: GS-6620; GS-6620 tablet, 100 mg QD, Fasted; Drug: GS-6620; GS-6620 tablet, 300 mg QD, Fasted; Drug: GS-6620; GS-6620 tablet, 900 mg QD, Fasted
Other: Cohort 5; Cohort 5 (N = 10, genotype 1): (Active drug: 8, Matching Placebo: 2) 300 mg GS 6620 or placebo QD in the morning without food (TDD = 300 mg) for 5 days	Drug: GS-6620; GS-6620 tablet, 50 mg QD; Drug: GS-6620; GS-6620 tablet, 100 mg QD; Drug: GS-6620; GS-6620 tablet, 300 mg QD; Drug: GS-6620; GS-6620 tablet, 100 mg QD, Fasted; Drug: GS-6620; GS-6620 tablet, 300 mg QD, Fasted; Drug: GS-6620; GS-6620 tablet, 900 mg QD, Fasted
Other: Cohort 6; Cohort 6 (N = 10, genotype 2 or genotype 3): (Active drug: 8, Matching Placebo: 2) 900 mg GS 6620 or placebo QD in the morning without food (TDD = 900 mg) for 5 days	Drug: GS-6620; GS-6620 tablet, 50 mg QD; Drug: GS-6620; GS-6620 tablet, 100 mg QD; Drug: GS-6620; GS-6620 tablet, 300 mg QD; Drug: GS-6620; GS-6620 tablet, 100 mg QD, Fasted; Drug: GS-6620; GS-6620 tablet, 300 mg QD, Fasted; Drug: GS-6620; GS-6620 tablet, 900 mg QD, Fasted
Other: Cohort 7; Cohort 7 (N = 10, genotype 1): (Active drug: 8, Matching Placebo: 2) 450 mg GS 6620 or placebo, administered BID with food (TDD = 900 mg) for 5 days	Drug: GS-6620 tablet, 450 mg BID; GS-6620 tablet, 450 mg BID
Other: Cohort 9; Cohort 9 (N = 10, genotype 1): (Active drug: 8, Matching Placebo: 2) 900 mg GS 6620 or placebo BID in the with food (TDD = 1800 mg) for 5 days	Drug: GS-6620 tablet; GS-6620 tablet, 900mg , BID; Drug: GS-6620 tablet; GS-6620 tablet, 900 mg
Other: Cohort 11; Cohort 11 (N = 10, genotype 1 : (Active drug: 8, Matching Placebo: 2) Up to 450 mg GS-6620 or placebo as an oral solution, BID, 12 hours apart in the fasted state, 2 hours after a meal (up to TDD = up to 900 mg) for 5 days.	Drug: GS-6620 tablet; GS-6620 tablet, 900mg , BID; Drug: GS-6620 tablet; GS-6620 tablet, 900 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Number of subjects with adverse events as a measure of safety and tolerability.
Number of subjects with HCV RNA viral response as a measure of antiviral activity.

Secondary Outcome Measures

Outcome Measure
Concentrations and pharmacokinetic parameters of GS-6620 and its metabolites will be measured.

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Investigators: Study Director: Stephen Rossi, PharmD, Gilead Sciences

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (Actual): October 1, 2011
• Study Completion (Actual): January 1, 2012

Study Registration Dates

• First Submitted: February 3, 2011
• First Submitted That Met QC Criteria: March 14, 2011
• First Posted (Estimate): March 16, 2011

Study Record Updates

• Last Update Posted (Estimate): March 26, 2012
• Last Update Submitted That Met QC Criteria: March 22, 2012
• Last Verified: March 1, 2012

More Information

Terms related to this study

• Keywords: HCV; Hepatitis C; HCV RNA; Polymerase inhibitor; Treatment naïve; GS-6620
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Hepatitis; Hepatitis A; Hepatitis C; Virus Diseases; Hepatitis C, Chronic
• Other Study ID Numbers: GS-US-119-0101