Double-Blind, Placebo-Controlled, Multiple Ascending Dose Study to Evaluate the Antiviral Activity and Safety, Tolerability, and Pharmacokinetics of Daclatasvir in Subjects Infected With Hepatitis C Virus Genotype 1
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 167
- 试验地点
- 8
- 主要终点
- Change From Baseline at Day 7 in log10 Hepatitis C Virus (HCV) RNA of All Participants
研究概览
简要总结
The primary purpose of this study is to assess the change in Hepatitis C Virus RNA during dosing with daclatasvir and during the follow-up period in subjects with chronic hepatitis C infection
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
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
- •Chronically infected with Hepatitis C Virus (HCV) genotype 1
- •Treatment naive or treatment non-responders or treatment intolerant; and not co-infected with HIV or Hepatitis B Virus
- •HCV RNA viral load of ≥10*5 IU/mL
- •BMI 18 to 35kg/m²
排除标准
- •Any significant acute or chronic medical illness which is not stable or is not controlled with medication and not consistent with Hepatitis C Virus infection
- •HIV and/or HBV positive
- •Major surgery within 4 weeks of study drug administration and any gastrointestinal surgery that could impact the absorption of study drug
- •WOCBP will be enrolled as in-patient for 16 days
研究组 & 干预措施
Group 6
Group 6: Active Comparator
Daclatasvir (1-100 mg), once or twice daily
or
Matching Placebo, once or twice daily
干预措施: Daclatasvir (Drug)
Group 1
Daclatasvir (1 mg), once daily
or
Matching Placebo, once daily
干预措施: Daclatasvir (Drug)
Group 1
Daclatasvir (1 mg), once daily
or
Matching Placebo, once daily
干预措施: Placebo (Drug)
Group 2
Daclatasvir (10 mg), once daily
or
Matching Placebo, once daily
干预措施: Daclatasvir (Drug)
Group 6
Group 6: Active Comparator
Daclatasvir (1-100 mg), once or twice daily
or
Matching Placebo, once or twice daily
干预措施: Placebo (Drug)
Group 2
Daclatasvir (10 mg), once daily
or
Matching Placebo, once daily
干预措施: Placebo (Drug)
Group 3
Daclatasvir (1-100 mg), once or twice daily
or
Matching Placebo, once or twice daily
干预措施: Daclatasvir (Drug)
Group 3
Daclatasvir (1-100 mg), once or twice daily
or
Matching Placebo, once or twice daily
干预措施: Placebo (Drug)
Group 4
Daclatasvir (1-100 mg), once or twice daily
or
Matching Placebo, once or twice daily
干预措施: Daclatasvir (Drug)
Group 4
Daclatasvir (1-100 mg), once or twice daily
or
Matching Placebo, once or twice daily
干预措施: Placebo (Drug)
Group 5
Group 5: Active Comparator
Daclatasvir (1-100 mg), once or twice daily
or
Matching Placebo, once or twice daily
干预措施: Daclatasvir (Drug)
Group 5
Group 5: Active Comparator
Daclatasvir (1-100 mg), once or twice daily
or
Matching Placebo, once or twice daily
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline at Day 7 in log10 Hepatitis C Virus (HCV) RNA of All Participants
时间窗: Baseline, Day 7
The Roche TaqMan HCV quantitative assay was used for analysis with detection limit of 10 IU/mL. Baseline was Day -1.
次要结局
- Change From Baseline at Day 7 in log10 Hepatitis C Virus (HCV) RNA Levels of Participants Without Baseline Drug Resistance(Baseline, Day 7)
- Change From Baseline to Day 14 in Log10 Hepatitis C Virus (HCV) RNA in Participants Without Baseline Drug Resistance(Baseline to Day 14)
- Change From Baseline at 24 h Post Dose on Day 1 in log10 Hepatitis C Virus (HCV) RNA of Participants Without Baseline Drug Resistance(Baseline, 2, 4, 6, 8, 12, 16, 20, and 24 hours post dose on Day 1)
- Change From Baseline to Day 4 in log10 Hepatitis C Virus (HCV) RNA in Participants Without Baseline Drug Resistance(Baseline to Day 4)
- Time to Maximum Decline From Baseline in Hepatitis C Virus (HCV) RNA in Participants Without Baseline Drug Resistance(Day 1 up to Day 14)
- Maximum Decline From Baseline in Log10 Hepatitis C Virus (HCV) RNA in Participants Without Baseline Drug Resistance(Day 1 up to Day 14)
- Maximum Observed Plasma Concentration (Cmax) and Minimum Observed Plasma Concentration (Cmin) of Daclatasvir on Days 1 and 14(0 hour (pre-dose) 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours (post morning dose) at Day1 and Day 14, 0 hour (pre-dose) at Days 2, 3, 4, 5, 7, 9, 11, 13 and 24, 48 and 72 hours (post morning dose) at Day 14)
- Area Under the Concentration-time Curve (AUC) in 1 Dosing Interval of Daclatasvir at Days 1 and 14(0 hour (pre-dose) 0.5, 1,1.5, 2, 3, 4, 6, 8 and 12 hours (post morning dose) at Day1 and Day 14, 0 hr (pre-dose) at Days 2, 3, 4, 5, 7, 9, 11, 13, and 24, 48 and 72 hours (post morning dose) at Day 14)
- Plasma Half-life (T-half) of Daclatasvir at Day 14(0 hour (pre-dose) 0.5, 1,1.5, 2, 3, 4, 6, 8 and 12 hours (post morning dose) at Day1 and Day 14, 0 hr (pre-dose) at Days 2, 3, 4, 5, 7, 9, 11, 13, and 24, 48 and 72 hours (post morning dose) at Day 14)
- Apparent Total Body Clearance (CLT/F) of Daclatasvir on Day 14(0 hour (pre-dose) 0.5, 1,1.5, 2, 3, 4, 6, 8 and 12 hours (post morning dose) at Day1 and Day 14, 0 hour (pre-dose) at Days 2, 3, 4, 5, 7, 9, 11, 13, and 24, 48 and 72 hours (post morning dose) at Day 14)
- Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters(Screening, Day 2, 3, 5, 7, 9, 11, 13, 15, 21 and 28)
- Average Observed Plasma Concentration (Css-av) at Steady State of Daclatasvir at Days 1 and 14(0 hour (pre-dose) 0.5, 1,1.5, 2, 3, 4, 6, 8 and 12 hours (post morning dose) at Day1 and Day 14, 0 hr (pre-dose) at Days 2, 3, 4, 5, 7, 9, 11,13, and 24, 48 and 72 hours (post morning dose) at Day 14)
- Accumulation Index (AI) AUC(TAU), AI Cmax, and Degree of Fluctuation (DF) of Daclatasvir on Day 14(0 hour (pre-dose) 0.5, 1,1.5, 2, 3, 4, 6, 8 and 12 hours (post morning dose) at Day1 and Day 14, 0 hour (pre-dose) at Days 2, 3, 4, 5, 7, 9, 11, 13, and 24, 48 and 72 hours (post morning dose) at Day 14)
- Time of Maximum Observed Plasma Concentration (Tmax) of Daclatasvir on Days 1 and 14(0 hour (pre-dose) 0.5, 1,1.5, 2, 3, 4, 6, 8 and 12 hours (post morning dose) at Day1 and Day 14, 0 hour (pre-dose) at Days 2, 3, 4, 5, 7, 9, 11, 13, and 24, 48 and 72 hours (post morning dose) at Day 14)
- Correlation Coefficients Between Measures of Decline in log10 Hepatitis C Virus (HCV) RNA and Daclatasvir PK Parameters Cmax, AUC(TAU), and Cmin on Day 14 in Participants Without Baseline Drug Resistance(Day 4, Day 14)
- Number of Participants With Serious Adverse Events (SAEs), Discontinuation Due to Adverse Events (AEs), and Who Died(Day 1 to Day 182 or Day of Discharge)
- Number of Participants With Marked Laboratory Abnormalities in Hematology(Screening, Day 3, Day 7, Day 11, Day 14, and Day 28)
- Number of Participants With Marked Abnormalities in Liver and Kidney Function Laboratory Tests and Electrolytes(Screening, Day 3, Day 7, Day 11, Day 14, and Day 28)
- Number of Participants With Marked Laboratory Abnormalities in Lipase and Glucose(Screening, Day 3, Day 7, Day 11, Day 14, and Day 28)
- Number of Participants With Marked Laboratory Abnormalities in Urinalysis(Screening, Day 3, Day 7, Day 11, Day 14, and Day 28)
- Number of Participants With Clinically Relevant Change From Baseline in Vital Signs(Screening, Day -1 and prior to morning dose on Day 1, 2, 14, and 28)