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

Gilead Sciences

Status and phase: Completed; Phase 1

Conditions: Hepatitis C, Chronic

Treatments: Drug: GS-6620 tablet, 450 mg BID; Drug: GS-6620; Drug: GS-6620 tablet

Study type: Interventional

Funder types: Industry

Identifiers

NCT01316237

GS-US-119-0101

Details and patient eligibility

About

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.

Enrollment: 90 estimated patients

Sex: All

Ages: 18 to 60 years old

Volunteers: No Healthy Volunteers

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

Trial design

90 participants in 9 patient groups

Cohort 1

Other group

Description:

(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

Treatment:

Drug: GS-6620

Drug: GS-6620

Drug: GS-6620

Drug: GS-6620

Drug: GS-6620

Drug: GS-6620

Cohort 2

Other group

Description:

(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

Treatment:

Drug: GS-6620

Drug: GS-6620

Drug: GS-6620

Drug: GS-6620

Drug: GS-6620

Drug: GS-6620

Cohort 3

Other group

Description:

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

Treatment:

Drug: GS-6620

Drug: GS-6620

Drug: GS-6620

Drug: GS-6620

Drug: GS-6620

Drug: GS-6620

Cohort 4

Other group

Description:

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

Treatment:

Drug: GS-6620

Drug: GS-6620

Drug: GS-6620

Drug: GS-6620

Drug: GS-6620

Drug: GS-6620

Cohort 5

Other group

Description:

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

Treatment:

Drug: GS-6620

Drug: GS-6620

Drug: GS-6620

Drug: GS-6620

Drug: GS-6620

Drug: GS-6620

Cohort 6

Other group

Description:

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

Treatment:

Drug: GS-6620

Drug: GS-6620

Drug: GS-6620

Drug: GS-6620

Drug: GS-6620

Drug: GS-6620

Cohort 7

Other group

Description:

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

Treatment:

Drug: GS-6620 tablet, 450 mg BID

Cohort 9

Other group

Description:

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

Treatment:

Drug: GS-6620 tablet

Drug: GS-6620 tablet

Cohort 11

Other group

Description:

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.

Treatment:

Drug: GS-6620 tablet

Drug: GS-6620 tablet