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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 90
- 试验地点
- 13
- 主要终点
- Number of subjects with adverse events as a measure of safety and tolerability.
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
研究组 & 干预措施
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
干预措施: GS-6620 (Drug)
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
干预措施: GS-6620 (Drug)
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
干预措施: GS-6620 (Drug)
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
干预措施: GS-6620 (Drug)
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
干预措施: GS-6620 (Drug)
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
干预措施: GS-6620 (Drug)
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
干预措施: GS-6620 tablet, 450 mg BID (Drug)
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
干预措施: GS-6620 tablet (Drug)
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.
干预措施: GS-6620 tablet (Drug)
结局指标
主要结局
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.
次要结局
- Concentrations and pharmacokinetic parameters of GS-6620 and its metabolites will be measured.