Antiviral Effect, Safety and Pharmacokinetics of BI 201335 NA in Hepatitis C Virus Genotype 1 Infected Treatment-naïve and Treatment-experienced Patients for 24 Weeks as Combination Therapy With Pegylated Interferon-alpha 2a and Ribavirin (Double-blinded, Randomised, Placebo-controlled, Phase II)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 719
- 试验地点
- 100
- 主要终点
- Virological Response 4 Weeks After the End of Treatment With BI 201335 or Placebo
研究概览
简要总结
The objective was to investigate the antiviral effect, safety, and pharmacokinetics of BI 201335 (Faldaprevir), given as a soft gelatine capsule, in patients with hepatitis C virus (HCV) genotype 1 infection. Combination therapy of BI 201335 (Faldaprevir) with pegylated interferon α-2a (PegIFN) and ribavirin (RBV), with or without a 3-day lead-in, was assessed in treatment-naïve (TN) and treatment experienced (TE) patients.
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
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
240 mg QD TN
240 mg BI 201335 NA (Faldaprevir) once daily (QD) combined with PegIFN/RBV for 24 weeks, success-dependently followed by re-randomisation to stop or to an additional 24 weeks of PegIFN/RBV in treatment-naive (TN) patients
干预措施: BI 201335 NA 240 mg QD (Drug)
240 mg QD TN
240 mg BI 201335 NA (Faldaprevir) once daily (QD) combined with PegIFN/RBV for 24 weeks, success-dependently followed by re-randomisation to stop or to an additional 24 weeks of PegIFN/RBV in treatment-naive (TN) patients
干预措施: PegIFN/RBV (Drug)
240 mg QD / LI-TN
240 mg BI 201335 NA (Faldaprevir) once daily (QD) combined with PegIFN/RBV for 24 weeks, with a 3-day lead-in phase of PegIFN/RBV (i.e. initiation of BI 201335 (Faldaprevir) three days after first administration of PegIFN/RBV), success-dependently followed by re-randomisation to stop or to an additional 24 weeks of PegIFN/RBV in treatment-naive (TN) patients
干预措施: BI 201335 NA 240 mg QD / LI (Drug)
240 mg QD / LI-TN
240 mg BI 201335 NA (Faldaprevir) once daily (QD) combined with PegIFN/RBV for 24 weeks, with a 3-day lead-in phase of PegIFN/RBV (i.e. initiation of BI 201335 (Faldaprevir) three days after first administration of PegIFN/RBV), success-dependently followed by re-randomisation to stop or to an additional 24 weeks of PegIFN/RBV in treatment-naive (TN) patients
干预措施: PegIFN/RBV (Drug)
Placebo
Placebo once daily combined with PegIFN/RBV for 24 weeks, followed by an additional 24 weeks of PegIFN/RBV in treatment-naive (TN) patients
干预措施: PegIFN/RBV (Drug)
Placebo
Placebo once daily combined with PegIFN/RBV for 24 weeks, followed by an additional 24 weeks of PegIFN/RBV in treatment-naive (TN) patients
干预措施: Placebo (Drug)
120 mg QD / LI-TN
120 mg BI 201335 NA (Faldaprevir) once daily (QD) combined with PegIFN/RBV for 24 weeks, with a 3-day lead-in (LI) phase of PegIFN/RBV (i.e. initiation of BI 201335 (Faldaprevir) three days after first administration of PegIFN/RBV), followed by an additional 24 weeks of PegIFN/RBV in treatment naive (TN) patients
干预措施: BI 201335 NA 120mg QD / LI (Drug)
120 mg QD / LI-TN
120 mg BI 201335 NA (Faldaprevir) once daily (QD) combined with PegIFN/RBV for 24 weeks, with a 3-day lead-in (LI) phase of PegIFN/RBV (i.e. initiation of BI 201335 (Faldaprevir) three days after first administration of PegIFN/RBV), followed by an additional 24 weeks of PegIFN/RBV in treatment naive (TN) patients
干预措施: PegIFN/RBV (Drug)
240 mg QD TE
240 mg BI 201335 NA (Faldaprevir) once daily (QD) combined with PegIFN/RBV for 24 weeks, followed by an additional 24 weeks of PegIFN/RBV in treatment experienced (TE) patients
干预措施: BI 201335 NA 240 mg QD (Drug)
240 mg QD TE
240 mg BI 201335 NA (Faldaprevir) once daily (QD) combined with PegIFN/RBV for 24 weeks, followed by an additional 24 weeks of PegIFN/RBV in treatment experienced (TE) patients
干预措施: PegIFN/RBV (Drug)
240 mg QD / LI-TE
240 mg BI 201335 NA (Faldaprevir) once daily (QD) combined with PegIFN/RBV for 24 weeks, with a 3-day lead-in phase of PegIFN/RBV (i.e. initiation of BI 201335 (Faldaprevir) three days after first administration of PegIFN/RBV), success-dependently followed by re-randomisation to stop or to an additional 24 weeks of PegIFN/RBV in treatment-experienced (TE) patients
干预措施: PegIFN/RBV (Drug)
240 mg QD / LI-TE
240 mg BI 201335 NA (Faldaprevir) once daily (QD) combined with PegIFN/RBV for 24 weeks, with a 3-day lead-in phase of PegIFN/RBV (i.e. initiation of BI 201335 (Faldaprevir) three days after first administration of PegIFN/RBV), success-dependently followed by re-randomisation to stop or to an additional 24 weeks of PegIFN/RBV in treatment-experienced (TE) patients
干预措施: BI 201335 NA 240 mg QD (Drug)
240 mg BID / LI-TE
240mg BI 201335 NA (Faldaprevir) twice daily combined with PegIFN/RBV for 24 or 48 weeks, with 3-day lead-in phase of PegIFN/RBV, in treatment-experienced patients
干预措施: BI 201335 NA 240 mg BID (Drug)
240 mg BID / LI-TE
240mg BI 201335 NA (Faldaprevir) twice daily combined with PegIFN/RBV for 24 or 48 weeks, with 3-day lead-in phase of PegIFN/RBV, in treatment-experienced patients
干预措施: PegIFN/RBV (Drug)
结局指标
主要结局
Virological Response 4 Weeks After the End of Treatment With BI 201335 or Placebo
时间窗: Week 28
An achieved virological response is defined as the plasma Hepatitis C Virus RiboNucleic Acid (HCV RNA) level below the lower limit of detection (BLD). This data was only collected for patients, who stopped trial participation at Week 24 and did not continue with PegIFN/RBV until Week 48. The lower limit of quantification (BLQ) of this assay was 25 IU/mL and the lower limit of detection (BLD) was 10 IU/mL at the time of the protocol finalisation. During the course of the trial, the manufacturer defined BLD as '\< 25 IU/mL, not detectable' and BLQ as '\< 25 IU/mL, detectable'.
Sustained Virological Response 24 Weeks (SVR24) After Completion of All Therapy
时间窗: Day 155 after the end of all treatment
Virological (VL) response was defined as the plasma HCV RNA level below the lower limit of detection. The first VL measurement that occurred in the time window ≥ Day 155 (from End Of Treatment on) was selected for the determination of SVR24. Therefore, patients with virological load BLD 24 weeks after completion of therapy, who had a rebound after this time point (outside the defined time window of 155 days after end of all treatments) were identified as SVR24 achieved.
次要结局
- Breakthrough on BI 201335/Placebo (Rebound While All 3 Treatments Were Still Ongoing)(Up to Week 24)
- Global Assessment of Tolerability(Week 24)
- Number of Patients [N(%)] With Transitions Relative to Reference Range for Laboratory Parameter Haemoglobin(Baseline and Week 24)
- Change From Baseline to Week 24 in Absolute Neutrophils of the Patients(Baseline and Week 24)
- Trough Concentration (Cpre,ss) of Faldaprevir at Steady State(Week 8, week 10, week 12, week 24)
- Breakthrough on PegIFN/RBV (Rebound While Only PegIFN/RBV Treatment Alone Was Still Ongoing)(Week 24 through Week 48)
- Change From Baseline to Week 24 in Diastolic Blood Pressure and Systolic Blood Pressure(Baseline and Week 24)
- Change From Baseline to Week 24 in Haemoglobin of the Patients(Baseline and Week 24)
- Number of Patients [N(%)] With Transitions Relative to Reference Range for Laboratory Parameter ALT/GPT,SGPT(Baseline and Week 24)
- Change From Baseline to Week 24 in Total Bilirubin of the Patients(Baseline and Week 24)
- Number of Patients [N(%)] With Transitions Relative to Reference Range for Laboratory Parameter Total Bilirubin(Baseline and Week 24)
- Virological Response at Week 4(Week 4)
- Time to Loss of Virological Response(Week 24)
- Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1000 mg/Day RBV)(Week 8, week 10, week 12, week 24)
- Complete Early Virological Response (cEVR)(Week 12)
- End of Treatment Response at Week 24(Week 24)
- Time to Reach a Plasma HCV RNA Level Below the Lower Limit of Detection(On or after day 155 post end of all treatment)
- Relapse(post-End of treatment (i.e. post 48 weeks))
- Change From Baseline to Week 24 in Pulse Rate(Baseline and Week 24)
- Change From Baseline to Week 24 in Weight of the Patients(Baseline and Week 24)
- Change From Baseline to Week 24 in ALT/GPT,SGPT of the Patients(Baseline and Week 24)
- Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1200 mg/Day RBV)(Week 8, week 10, week 12, week 24)
- Trough Concentration (Cpre,ss) of PegIFN at Steady State(Week 8, week 10, week 12, week 24)
- Virological Response at Week 2(Week 2)
- Early Virological Response (EVR)(Baseline and Week 12)
- Extended Rapid Virological Response (eRVR)(Week 4 and Week 12)
- End of Treatment Response at End of All Therapy(Week 24 or Week 48)
- Sustained Virological Response 12 Weeks (SVR12) After Completion of All Therapy(Week 36 or Week 60)
- Virological Rebound(Week 24 or Week 48)
- Number of Patients [N(%)] With Transitions Relative to Reference Range for Laboratory Parameter Absolute Neutrophils(Baseline and Week 24)