A Multi-center, Double-Blind, Parallel Group, Randomized, Placebo-Controlled, Dose Ranging Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Following Oral Administration of PSI-7977 in Combination With Standard of Care (Pegylated Interferon and Ribavirin) in Treatment-Naïve Patients With Chronic HCV Infection Genotype 1
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 64
- 试验地点
- 7
- 主要终点
- Percentage of Participants Who Experienced Adverse Events During the Sofosbuvir Treatment Period
研究概览
简要总结
Participants with genotype 1 HCV infection were randomized to 1 of 3 sofosbuvir doses (100 mg, 200 mg, or 400 mg) or matching placebo once daily based upon stratification for IL28B status (CC or CT/TT). Placebo tablets were administered to participants receiving 100 mg active sofosbuvir (3 placebo tablets) and 200 mg active sofosbuvir (2 placebo tablets) in order to maintain the study blind. Participants received sofosbuvir/matching placebo from Day 0 to 27. Participants also received treatment with PEG+RBV starting on Day 0 of the study which continued for 48 weeks. Participants were evaluated for sustained virologic response (SVR) for an additional 24 weeks following completion of study treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Treatment-naive males and females, 18-65 years of age
- •Genotype 1 HCV infection
- •Negative pregnancy test for females of childbearing age
- •Females of childbearing age and males with female partners of childbearing age must use two forms of contraception during treatment and following the last dose of ribavirin in accordance with locally approved label for ribavirin
排除标准
- •Hepatitis B or HIV infection
- •Pregnant or breast feeding females or male partners of pregnant females
- •Previous interferon or ribavirin-based therapy or investigational anti-HCV agent
- •History or evidence of medical condition associated with chronic liver disease other than HCV
研究组 & 干预措施
Sofosbuvir 100 mg+PEG+RBV
Participants received sofosbuvir 100 mg (1 x 100 mg tablet) and placebo to match sofosbuvir (3 tablets) for 28 days (baseline to Day 28), plus PEG+RBV (baseline to Week 48)
干预措施: PEG (Drug)
Sofosbuvir 100 mg+PEG+RBV
Participants received sofosbuvir 100 mg (1 x 100 mg tablet) and placebo to match sofosbuvir (3 tablets) for 28 days (baseline to Day 28), plus PEG+RBV (baseline to Week 48)
干预措施: Sofosbuvir (Drug)
Sofosbuvir 100 mg+PEG+RBV
Participants received sofosbuvir 100 mg (1 x 100 mg tablet) and placebo to match sofosbuvir (3 tablets) for 28 days (baseline to Day 28), plus PEG+RBV (baseline to Week 48)
干预措施: RBV (Drug)
Sofosbuvir 200 mg+PEG+RBV
Participants received sofosbuvir 200 mg (2 x 100 mg tablets) and placebo to match sofosbuvir (2 tablets) for 28 days (baseline to Day 28), plus PEG+RBV (baseline to Week 48)
干预措施: Sofosbuvir (Drug)
Sofosbuvir 200 mg+PEG+RBV
Participants received sofosbuvir 200 mg (2 x 100 mg tablets) and placebo to match sofosbuvir (2 tablets) for 28 days (baseline to Day 28), plus PEG+RBV (baseline to Week 48)
干预措施: PEG (Drug)
Sofosbuvir 200 mg+PEG+RBV
Participants received sofosbuvir 200 mg (2 x 100 mg tablets) and placebo to match sofosbuvir (2 tablets) for 28 days (baseline to Day 28), plus PEG+RBV (baseline to Week 48)
干预措施: RBV (Drug)
Sofosbuvir 400 mg+PEG+RBV
Participants received sofosbuvir 400 mg (4 x 100 mg tablets) for 28 days (baseline to Day 28), plus PEG+RBV (baseline to Week 48)
干预措施: Sofosbuvir (Drug)
Sofosbuvir 400 mg+PEG+RBV
Participants received sofosbuvir 400 mg (4 x 100 mg tablets) for 28 days (baseline to Day 28), plus PEG+RBV (baseline to Week 48)
干预措施: PEG (Drug)
Sofosbuvir 400 mg+PEG+RBV
Participants received sofosbuvir 400 mg (4 x 100 mg tablets) for 28 days (baseline to Day 28), plus PEG+RBV (baseline to Week 48)
干预措施: RBV (Drug)
Placebo+PEG+RBV
Participants received placebo to match sofosbuvir (4 tablets) for 28 days (baseline to Day 28), plus PEG+RBV (baseline to Week 48)
干预措施: Placebo (Drug)
Placebo+PEG+RBV
Participants received placebo to match sofosbuvir (4 tablets) for 28 days (baseline to Day 28), plus PEG+RBV (baseline to Week 48)
干预措施: PEG (Drug)
Placebo+PEG+RBV
Participants received placebo to match sofosbuvir (4 tablets) for 28 days (baseline to Day 28), plus PEG+RBV (baseline to Week 48)
干预措施: RBV (Drug)
结局指标
主要结局
Percentage of Participants Who Experienced Adverse Events During the Sofosbuvir Treatment Period
时间窗: Baseline to Week 4
Adverse events (AEs) occurring during the sofosbuvir treatment period were summarized across the participant population. A participant was counted once if they had a qualifying event.
次要结局
- Change in Circulating HCV RNA at Week 4(Baseline to Week 4)
- Percentage of Participants With Rapid Virologic Response at Week 4(Week 4)
- Percentage of Participants With Sustained Virologic Response (SVR) at 12 and 24 Weeks After Last Dose of PEG+RBV Following Completion of 48 Weeks of Treatment(Post-treatment Weeks 12 and 24)
- Plasma Pharmacokinetics of Sofosbuvir: Cmax at Day 0(Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose)
- Plasma Pharmacokinetics of Sofosbuvir: Cmax at Day 27(Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose))
- Plasma Pharmacokinetics of GS-331007: AUCtau at Day 27(Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose))
- Plasma Pharmacokinetics of GS-566500: Cmax at Day 0(Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose)
- Plasma Pharmacokinetics of GS-566500: Cmax at Day 27(Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose))
- Plasma Pharmacokinetics of GS-566500: AUCinf at Day 0(Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose)
- Plasma Pharmacokinetics of GS-566500: AUCtau at Day 27(Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose))
- Percentage of Participants Who Developed Resistance to Sofosbuvir(Baseline to Week 4)
- Plasma Pharmacokinetics of Sofosbuvir: AUCinf at Day 0(Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose)
- Plasma Pharmacokinetics of Sofosbuvir: AUCtau at Day 27(Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose))
- Plasma Pharmacokinetics of GS-331007: Cmax at Day 0(Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose)
- Plasma Pharmacokinetics of GS-331007: Cmax at Day 27(Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose))
- Plasma Pharmacokinetics of GS-331007: AUCinf at Day 0(Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose)