A Phase 2b, Open-Label Study of 200 mg or 400 mg Sofosbuvir+RBV for 24 Weeks in Genotype 1 or 3 and Ledipasvir/Sofosbuvir (LDV/SOF) Fixed Dose Combination (FDC) Tablet for 12 Weeks in Genotype 1 or 4 HCV Infected Subjects With Renal Insufficiency
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 38
- 主要终点
- Percentage of Participants Experiencing Treatment-Emergent Adverse Events
研究概览
简要总结
The primary objectives of this study are to evaluate the safety and efficacy of sofosbuvir (SOF) plus ribavirin (RBV) for 24 weeks and ledipasvir/sofosbuvir (LDV/SOF) for 12 weeks, and to evaluate the steady state pharmacokinetics (PK) of SOF and its metabolites and LDV in participants with genotype (GT) 1, 3, or 4 hepatitis C virus (HCV) infection who have chronic renal insufficiency (impaired kidney function).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Cohorts 1 and 2: chronic genotype 1 or 3 HCV infection
- •Cohort 3: chronic genotype 1 or 4 HCV infection
- •HCV RNA ≥ 10^4 IU/mL at screening
- •Screening labs within defined thresholds
- •Cirrhosis determination at screening
排除标准
- •Females who are pregnant or nursing or males who have a pregnant partner
- •Prior null response to pegylated interferon (Peg-IFN)+RBV therapy (Cohorts 1 and 2) or for individuals with cirrhosis, prior treatment failure with IFN-based therapy not resulting from treatment intolerance (Cohort 3)
- •Current of prior history of hepatic decompensation
- •Infection with hepatitis B virus (HBV) or HIV
- •History of clinically significant illness (including psychiatric or cardiac) or any other medical disorder that may interfere with individual's treatment and/or adherence to the protocol
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
SOF 200 mg + RBV 200 mg (Cohort 1)
Participants with genotype 1 or 3 HCV infection will receive SOF 200 mg (2 × 100 mg tablets) plus RBV once daily for 24 weeks.
干预措施: SOF (Drug)
SOF 200 mg + RBV 200 mg (Cohort 1)
Participants with genotype 1 or 3 HCV infection will receive SOF 200 mg (2 × 100 mg tablets) plus RBV once daily for 24 weeks.
干预措施: RBV (Drug)
SOF 400 mg + RBV 200 mg (Cohort 2)
Participants with genotype 1 or 3 HCV infection will receive SOF 400 mg (4 × 100 mg tablets or 1 × 400 mg tablet) plus RBV once daily for 24 weeks.
干预措施: SOF (Drug)
SOF 400 mg + RBV 200 mg (Cohort 2)
Participants with genotype 1 or 3 HCV infection will receive SOF 400 mg (4 × 100 mg tablets or 1 × 400 mg tablet) plus RBV once daily for 24 weeks.
干预措施: RBV (Drug)
LDV/SOF (Cohort 3)
Participants with genotype 1 or 4 HCV infection will receive LDV/SOF once daily for 12 weeks.
干预措施: LDV/SOF (Drug)
结局指标
主要结局
Percentage of Participants Experiencing Treatment-Emergent Adverse Events
时间窗: Up to 24 weeks plus 30 days
Pharmacokinetic (PK) Parameter: AUCtau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)
时间窗: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2
AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
PK Parameter: Cmax of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)
时间窗: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4
Cmax is defined as the maximum concentration of drug.
PK Parameter: AUCtau of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)
时间窗: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4
AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
PK Parameter: Cmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)
时间窗: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12
Cmax is defined as the maximum concentration of drug.
Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities
时间窗: Up to 24 weeks plus 30 days
Treatment-emergent laboratory abnormalities were defined as values that increased by at least 1 toxicity grade from baseline at any time postbaseline up to the date of last dose of study drug plus 30 days.
Percentage of Participants Experiencing Clinically Significant 12-lead Electrocardiogram (ECG) Abnormalities
时间窗: Up to 24 weeks plus 30 days
PK Parameter: Cmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)
时间窗: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2
Cmax is defined as the maximum concentration of drug.
PK Parameter: AUCtau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)
时间窗: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12
AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
PK Parameter: Ctau of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)
时间窗: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4
Ctau is defined as the observed drug concentration at the end of the dosing interval.
Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)
时间窗: Posttreatment Week 12
SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ; ie, 15 IU/mL) at 12 weeks after stopping study treatment.
Percentage of Participants Experiencing Treatment-Emergent Adverse Events Associated With Vital Sign Abnormalities
时间窗: Up to 24 weeks plus 30 days
PK Parameter: Ctau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)
时间窗: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2
Ctau is defined as the observed drug concentration at the end of the dosing interval.
PK Parameter: Ctau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)
时间窗: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12
Ctau is defined as the observed drug concentration at the end of the dosing interval.
次要结局
- Percentage of Participants With SVR at 24 Weeks After Discontinuation of Therapy (SVR24)(Posttreatment Week 24)
- Percentage of Participants With Overall Virologic Failure(Up to Posttreatment Week 24)
- PK Parameter: λz of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)(Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2)
- PK Parameter: t1/2 of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)(Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2)
- PK Parameter: t1/2 of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)(Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12)
- PK Parameter: AUClast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)(Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2)
- PK Parameter: AUClast of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)(Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4)
- PK Parameter: Clast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)(Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2)
- PK Parameter: Clast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)(Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12)
- PK Parameter: Tlast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)(Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12)
- PK Parameter: t1/2 of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)(Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4)
- PK Parameter: Clast of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)(Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4)
- PK Parameter: Tmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)(Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2)
- PK Parameter: Tmax of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)(Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4)
- PK Parameter: Tlast of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)(Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4)
- PK Parameter: λz of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)(Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12)
- Percentage of Participants With SVR at 4 Weeks After Discontinuation of Therapy (SVR4)(Posttreatment Week 4)
- PK Parameter: AUClast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)(Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12)
- PK Parameter: Tmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)(Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12)
- PK Parameter: Tlast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)(Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2)
- PK Parameter: λz of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)(Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4)