Antiviral Effect, Safety, and Pharmacokinetics of BI201335 +PegIFN/RBV in HCV-GT1 (SILEN-C1&2)
- Conditions
- Hepatitis C, Chronic
- Interventions
- Drug: BI 201335 NA 120mg QD / LIDrug: PegIFN/RBVDrug: BI 201335 NA 240 mg QDDrug: BI 201335 NA 240 mg QD / LIDrug: BI 201335 NA 240 mg BIDDrug: Placebo
- Registration Number
- NCT00774397
- Lead Sponsor
- Boehringer Ingelheim
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 719
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 120 mg QD / LI-TN BI 201335 NA 120mg QD / LI 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 Placebo PegIFN/RBV Placebo once daily combined with PegIFN/RBV for 24 weeks, followed by an additional 24 weeks of PegIFN/RBV in treatment-naive (TN) patients 240 mg QD TN BI 201335 NA 240 mg QD 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 240 mg QD / LI-TN BI 201335 NA 240 mg QD / LI 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 240 mg QD / LI-TN PegIFN/RBV 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 240 mg QD TE PegIFN/RBV 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 240 mg QD TE BI 201335 NA 240 mg QD 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 240 mg QD / LI-TE PegIFN/RBV 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 240 mg QD TN PegIFN/RBV 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 Placebo 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 120 mg QD / LI-TN PegIFN/RBV 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 240 mg QD / LI-TE BI 201335 NA 240 mg QD 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 240 mg BID / LI-TE BI 201335 NA 240 mg BID 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 240 mg BID / LI-TE PegIFN/RBV 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
- Primary Outcome Measures
Name Time Method Virological Response 4 Weeks After the End of Treatment With BI 201335 or Placebo 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 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.
- Secondary Outcome Measures
Name Time Method Breakthrough on BI 201335/Placebo (Rebound While All 3 Treatments Were Still Ongoing) Up to Week 24 Number of patients with Unconfirmed rebound ( ≥ 1log10 increase in HCV mRNA) while on BI201335/placebo + 5 days washout.
Global Assessment of Tolerability Week 24 The investigator was to assess the tolerability of trial medication based on adverse events (AEs) and the laboratory evaluation.
Tolerability was assessed by the investigator according to the categories 'good', 'satisfactory', 'not satisfactory', and 'bad'.Number of Patients [N(%)] With Transitions Relative to Reference Range for Laboratory Parameter Haemoglobin Baseline and Week 24 Number of patients with normal or high baseline moved to low .
Change From Baseline to Week 24 in Absolute Neutrophils of the Patients Baseline and Week 24 Baseline is defined as the last value before the administration of BI 201335 or placebo.
Trough Concentration (Cpre,ss) of Faldaprevir at Steady State Week 8, week 10, week 12, week 24 C(pre,ss) is defined as pre-dose (trough) concentration of Faldaprevir in plasma at steady state immediately before administration of the next dose.
Breakthrough on PegIFN/RBV (Rebound While Only PegIFN/RBV Treatment Alone Was Still Ongoing) Week 24 through Week 48 Number of patients with Unconfirmed rebound (≥ 1log10 increase in HCV mRNA) while on PegIFN/RBV treatment + 5 days washout.
Change From Baseline to Week 24 in Diastolic Blood Pressure and Systolic Blood Pressure Baseline and Week 24 Baseline is defined as the last value before the initial drug administration of BI 201335 or placebo.
Change From Baseline to Week 24 in Haemoglobin of the Patients Baseline and Week 24 Baseline is defined as the last value before the administration of BI 201335 or placebo.
Number of Patients [N(%)] With Transitions Relative to Reference Range for Laboratory Parameter ALT/GPT,SGPT Baseline and Week 24 Number of patients with normal or low baseline moved to high .
Change From Baseline to Week 24 in Total Bilirubin of the Patients Baseline and Week 24 Baseline is defined as the last value before the administration of BI 201335 or placebo.
Number of Patients [N(%)] With Transitions Relative to Reference Range for Laboratory Parameter Total Bilirubin Baseline and Week 24 Number of patients with normal or low baseline moved to high .
Virological Response at Week 4 Week 4 Viral load (plasma HCV RNA level) below the lower limit of quantification at Week 4 (\< 25 IU/ml, detectable or undetectable)
Time to Loss of Virological Response Week 24 Time to loss of virological response, defined as the last value below the lower limit of detection in a patient who subsequently had 2 consecutive plasma HCV RNA level measurements ≥100 IU/mL. Patients that did not achieve suppression of plasma HCV RNA levels below the lower limit of detection until Week 24 were defined as having a time to failure of zero.
Time is expressed in Median number of days.Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1000 mg/Day RBV) Week 8, week 10, week 12, week 24 C(pre,ss) is defined as pre-dose (trough) concentration of Ribavirin in plasma at steady state immediately before administration of the next dose.
Complete Early Virological Response (cEVR) Week 12 Complete Early Virological Response (cEVR) is defined as plasma HCV RNA level below the lower limit of detection at Week 12
End of Treatment Response at Week 24 Week 24 End of Treatment Response of BI 201335 or placebo (ETR BI 201335/placebo ) is defined as plasma HCV RNA level below the lower limit of detection at 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 Summary of time (i.e Median number of days) to reach a plasma HCV RNA level below limit of detection (BLD)
Relapse post-End of treatment (i.e. post 48 weeks) Relapse was rebound after the viral load at end of all treatment had been below the lower limit of detection, or, if the value at end of all treatment was missing, after both the last value before End of Treatment (EOT) and the first value after End of Treatment were below the lower limit of detection.
Patients could experience relapse at any point post-treatment.Change From Baseline to Week 24 in Pulse Rate Baseline and Week 24 Baseline is defined as the last value before the administration of BI 201335 or placebo.
Change From Baseline to Week 24 in Weight of the Patients Baseline and Week 24 Baseline is defined as the last value before the administration of BI 201335 or placebo.
Change From Baseline to Week 24 in ALT/GPT,SGPT of the Patients Baseline and Week 24 Baseline is defined as the last value before the drug administration of BI 201335 or placebo.
Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1200 mg/Day RBV) Week 8, week 10, week 12, week 24 C(pre,ss) is defined as pre-dose (trough) concentration of Ribavirin in plasma at steady state immediately before administration of the next dose.
Trough Concentration (Cpre,ss) of PegIFN at Steady State Week 8, week 10, week 12, week 24 C(pre,ss) is defined as pre-dose (trough) concentration of PegIFN in plasma at steady state immediately before administration of the next dose.
Virological Response at Week 2 Week 2 Viral load (plasma HCV RNA level) below the lower limit of quantification at Week 2 (\< 25 IU/ml, detectable or undetectable)
Early Virological Response (EVR) Baseline and Week 12 Early Virological Response (EVR) is defined as ≥ 2 log 10 reduction in plasma HCV RNA level from baseline at Week 12
Extended Rapid Virological Response (eRVR) Week 4 and Week 12 Extended Rapid Virological Response (eRVR) is defined as plasma HCV RNA levels below the lower limit of quantification at Week 4 and below the lower limit of detection at Week 12
End of Treatment Response at End of All Therapy Week 24 or Week 48 End of Treatment Response (ETR) is defined as plasma HCV RNA level below the lower limit of detection at end of all therapy, i.e. at Week 24 or Week 48
Sustained Virological Response 12 Weeks (SVR12) After Completion of All Therapy Week 36 or Week 60 Sustained Virological Response 12 Weeks (SVR12) after completion of all therapy is defined as plasma HCV RNA level below the lower limit of detection at 12 weeks after completion of all therapy, i.e. at Week 36 or 60
Virological Rebound Week 24 or Week 48 Virological rebound is defined as increase of ≥ 1 log 10 in plasma HCV RNA level from a quantifiable nadir, or to ≥ 250 IU/mL after previous nadir \< 25 IU/mL (detectable), or to ≥ 100 IU/mL after a previous viral load below the lower limit of detection.
Note that this is numerical rebound, not requiring confirmation with a re-measurement.Number of Patients [N(%)] With Transitions Relative to Reference Range for Laboratory Parameter Absolute Neutrophils Baseline and Week 24 Number of patients with normal or high baseline moved to low .
Trial Locations
- Locations (100)
1220.5.4302 Boehringer Ingelheim Investigational Site
🇦🇹Wien, Austria
1220.5.0008 Boehringer Ingelheim Investigational Site
🇺🇸San Francisco, California, United States
1220.5.0001 Boehringer Ingelheim Investigational Site
🇺🇸San Francisco, California, United States
1220.5.0005 Boehringer Ingelheim Investigational Site
🇺🇸Chicago, Illinois, United States
1220.5.0002 Boehringer Ingelheim Investigational Site
🇺🇸New York, New York, United States
1220.5.0006 Boehringer Ingelheim Investigational Site
🇺🇸Lutherville, Maryland, United States
1220.5.0003 Boehringer Ingelheim Investigational Site
🇺🇸New York, New York, United States
1220.5.0007 Boehringer Ingelheim Investigational Site
🇺🇸Philadelphia, Pennsylvania, United States
1220.5.0010 Boehringer Ingelheim Investigational Site
🇺🇸Germantown, Tennessee, United States
1220.5.0004 Boehringer Ingelheim Investigational Site
🇺🇸Austin, Texas, United States
1220.5.5401 Boehringer Ingelheim Investigational Site
🇦🇷Capital Federal, Argentina
1220.5.5403 Boehringer Ingelheim Investigational Site
🇦🇷Capital Federal, Argentina
1220.5.6110 Boehringer Ingelheim Investigational Site
🇦🇺Camperdown, New South Wales, Australia
1220.5.5402 Boehringer Ingelheim Investigational Site
🇦🇷Rosario, Argentina
1220.5.5405 Boehringer Ingelheim Investigational Site
🇦🇷Derqui, Pilar, Argentina
1220.5.6109 Boehringer Ingelheim Investigational Site
🇦🇺Kogarah, New South Wales, Australia
1220.5.5406 Boehringer Ingelheim Investigational Site
🇦🇷Rosario, Argentina
1220.5.6101 Boehringer Ingelheim Investigational Site
🇦🇺Westmead, New South Wales, Australia
1220.5.6105 Boehringer Ingelheim Investigational Site
🇦🇺Randwick, New South Wales, Australia
1220.5.6104 Boehringer Ingelheim Investigational Site
🇦🇺Woolloongabba, Queensland, Australia
1220.5.6103 Boehringer Ingelheim Investigational Site
🇦🇺Herston, Queensland, Australia
1220.5.6102 Boehringer Ingelheim Investigational Site
🇦🇺Clayton, Victoria, Australia
1220.5.6107 Boehringer Ingelheim Investigational Site
🇦🇺Fitzroy, Victoria, Australia
1220.5.6108 Boehringer Ingelheim Investigational Site
🇦🇺Parkville, Victoria, Australia
1220.5.4303 Boehringer Ingelheim Investigational Site
🇦🇹Linz, Austria
1220.5.4301 Boehringer Ingelheim Investigational Site
🇦🇹Wien, Austria
1220.5.1003 Boehringer Ingelheim Investigational Site
🇨🇦Edmonton, Alberta, Canada
1220.5.1007 Boehringer Ingelheim Investigational Site
🇨🇦Vancouver, British Columbia, Canada
1220.5.1006 Boehringer Ingelheim Investigational Site
🇨🇦Hamilton, Ontario, Canada
1220.5.1001 Boehringer Ingelheim Investigational Site
🇨🇦Ottawa, Ontario, Canada
1220.5.1002 Boehringer Ingelheim Investigational Site
🇨🇦Toronto, Ontario, Canada
1220.5.1004 Boehringer Ingelheim Investigational Site
🇨🇦Montreal, Quebec, Canada
1220.5.4202 Boehringer Ingelheim Investigational Site
🇨🇿Melnik, Czech Republic
1220.5.4203 Boehringer Ingelheim Investigational Site
🇨🇿Opava, Czech Republic
1220.5.3301A Boehringer Ingelheim Investigational Site
🇫🇷Clichy, France
1220.5.3307A Boehringer Ingelheim Investigational Site
🇫🇷Creteil, France
1220.5.3309A Boehringer Ingelheim Investigational Site
🇫🇷Lyon, France
1220.5.3304A Boehringer Ingelheim Investigational Site
🇫🇷Marseille, France
1220.5.3306A Boehringer Ingelheim Investigational Site
🇫🇷Montpellier, France
1220.5.3308A Boehringer Ingelheim Investigational Site
🇫🇷Paris Cedex 20, France
1220.5.3302A Boehringer Ingelheim Investigational Site
🇫🇷Paris, France
1220.5.3303A Boehringer Ingelheim Investigational Site
🇫🇷Paris, France
1220.5.3305A Boehringer Ingelheim Investigational Site
🇫🇷Vandoeuvre Cedex, France
1220.5.4903 Boehringer Ingelheim Investigational Site
🇩🇪Berlin, Germany
1220.5.4917 Boehringer Ingelheim Investigational Site
🇩🇪Berlin, Germany
1220.5.4914 Boehringer Ingelheim Investigational Site
🇩🇪Bochum, Germany
1220.5.4913 Boehringer Ingelheim Investigational Site
🇩🇪Bonn, Germany
1220.5.4915 Boehringer Ingelheim Investigational Site
🇩🇪Dortmund, Germany
1220.5.4908 Boehringer Ingelheim Investigational Site
🇩🇪Hamburg, Germany
1220.5.4912 Boehringer Ingelheim Investigational Site
🇩🇪Düsseldorf, Germany
1220.5.4905 Boehringer Ingelheim Investigational Site
🇩🇪Düsseldorf, Germany
1220.5.4904 Boehringer Ingelheim Investigational Site
🇩🇪Hannover, Germany
1220.5.4910 Boehringer Ingelheim Investigational Site
🇩🇪Leipzig, Germany
1220.5.4906 Boehringer Ingelheim Investigational Site
🇩🇪Frankfurt/Main, Germany
1220.5.4909 Boehringer Ingelheim Investigational Site
🇩🇪Mainz, Germany
1220.5.4907 Boehringer Ingelheim Investigational Site
🇩🇪Tübingen, Germany
1220.5.8210 Boehringer Ingelheim Investigational Site
🇰🇷Busan, Korea, Republic of
1220.5.8201 Boehringer Ingelheim Investigational Site
🇰🇷Pusan, Korea, Republic of
1220.5.8205 Boehringer Ingelheim Investigational Site
🇰🇷Daegu, Korea, Republic of
1220.5.8202 Boehringer Ingelheim Investigational Site
🇰🇷Seoul, Korea, Republic of
1220.5.8206 Boehringer Ingelheim Investigational Site
🇰🇷Seoul, Korea, Republic of
1220.5.8207 Boehringer Ingelheim Investigational Site
🇰🇷Seoul, Korea, Republic of
1220.5.8208 Boehringer Ingelheim Investigational Site
🇰🇷Seoul, Korea, Republic of
1220.5.8204 Boehringer Ingelheim Investigational Site
🇰🇷Seoungnam, Korea, Republic of
1220.5.8203 Boehringer Ingelheim Investigational Site
🇰🇷Sungnam, Korea, Republic of
1220.5.8209 Boehringer Ingelheim Investigational Site
🇰🇷Suwon, Korea, Republic of
1220.5.3101 Boehringer Ingelheim Investigational Site
🇳🇱Amsterdam, Netherlands
1220.5.8211 Boehringer Ingelheim Investigational Site
🇰🇷Yangsan, Korea, Republic of
1220.5.3102 Boehringer Ingelheim Investigational Site
🇳🇱Leiden, Netherlands
1220.5.3501 Boehringer Ingelheim Investigational Site
🇵🇹Coimbra, Portugal
1220.5.3504 Boehringer Ingelheim Investigational Site
🇵🇹Coimbra, Portugal
1220.5.3503 Boehringer Ingelheim Investigational Site
🇵🇹Lisboa, Portugal
1220.5.3502 Boehringer Ingelheim Investigational Site
🇵🇹Lisboa, Portugal
1220.5.3506 Boehringer Ingelheim Investigational Site
🇵🇹Porto, Portugal
1220.5.3507 Boehringer Ingelheim Investigational Site
🇵🇹Porto, Portugal
1220.5.4001 Boehringer Ingelheim Investigational Site
🇷🇴Bucharest, Romania
1220.5.4002 Boehringer Ingelheim Investigational Site
🇷🇴Bucharest, Romania
1220.5.3402 Boehringer Ingelheim Investigational Site
🇪🇸Barcelona, Spain
1220.5.3405 Boehringer Ingelheim Investigational Site
🇪🇸Barcelona, Spain
1220.5.3401 Boehringer Ingelheim Investigational Site
🇪🇸Madrid, Spain
1220.5.3403 Boehringer Ingelheim Investigational Site
🇪🇸Madrid, Spain
1220.5.3404 Boehringer Ingelheim Investigational Site
🇪🇸Madrid, Spain
1220.5.3406 Boehringer Ingelheim Investigational Site
🇪🇸Madrid, Spain
1220.5.4104 Boehringer Ingelheim Investigational Site
🇨🇭Bern, Switzerland
1220.5.4102 Boehringer Ingelheim Investigational Site
🇨🇭La Chaux-de-Fonds, Switzerland
1220.5.4103 Boehringer Ingelheim Investigational Site
🇨🇭Lugano, Switzerland
1220.5.4101 Boehringer Ingelheim Investigational Site
🇨🇭Zürich, Switzerland
1220.5.4405 Boehringer Ingelheim Investigational Site
🇬🇧Bristol, United Kingdom
1220.5.4401 Boehringer Ingelheim Investigational Site
🇬🇧London, United Kingdom
1220.5.4106 Boehringer Ingelheim Investigational Site
🇨🇭Zürich, Switzerland
1220.5.4402 Boehringer Ingelheim Investigational Site
🇬🇧London, United Kingdom
1220.5.4406 Boehringer Ingelheim Investigational Site
🇬🇧London, United Kingdom
1220.5.4408 Boehringer Ingelheim Investigational Site
🇬🇧Nottingham, United Kingdom
1220.5.4403 Boehringer Ingelheim Investigational Site
🇬🇧Southampton, United Kingdom
1220.5.4410 Boehringer Ingelheim Investigational Site
🇬🇧London, United Kingdom
1220.5.4409 Boehringer Ingelheim Investigational Site
🇬🇧London, United Kingdom
1220.5.4902 Boehringer Ingelheim Investigational Site
🇩🇪Berlin, Germany
1220.5.0009 Boehringer Ingelheim Investigational Site
🇺🇸Nashville, Tennessee, United States
1220.5.4003 Boehringer Ingelheim Investigational Site
🇷🇴Bucharest, Romania
1220.5.4004 Boehringer Ingelheim Investigational Site
🇷🇴Bucharest, Romania