Antiviral Effect, Safety, and Pharmacokinetics of BI201335 +PegIFN/RBV in HCV-GT1 (SILEN-C1&2)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00774397
First received: October 16, 2008
Last updated: October 14, 2015
Last verified: October 2015
Results First Received: July 3, 2015  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double-Blind;   Primary Purpose: Treatment
Condition: Hepatitis C, Chronic
Interventions: Drug: BI 201335 NA 240 mg QD / LI
Drug: PegIFN/RBV
Drug: BI 201335 NA 120mg QD / LI
Drug: BI 201335 NA 240 mg QD
Drug: BI 201335 NA 240 mg BID
Drug: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Placebo-TN

Placebo once daily combined with PegIFN/RBV for 24 weeks, followed by an additional 24 weeks of PegIFN/RBV in treatment-naive (TN) patients

[PegIFN/RBV (Pegylated interferon α-2a (Pegasys®)/ Ribavirin (Copegus®)): PegIFN (180 µg/wk) and RBV (1000/1200mg/d)]

120 mg QD / LI-TN

120 mg BI 201335 (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 three days after first administration of PegIFN/RBV), followed by an additional 24 weeks of PegIFN/RBV in treatment naive (TN) patients

[PegIFN/RBV: PegIFN (180 µg/wk) and RBV (1000/1200mg/d)]

240 mg QD / LI-TN

240 mg BI 201335 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 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

[PegIFN/RBV: PegIFN (180 µg/wk) and RBV (1000/1200mg/d)]

240 mg QD-TN

240 mg BI 201335 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

[PegIFN/RBV: PegIFN (180 µg/wk) and RBV (1000/1200mg/d)]

240 mg QD / LI-TE

240 mg BI 201335 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 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

[PegIFN/RBV: PegIFN (180 µg/wk) and RBV (1000/1200mg/d)]

240 mg QD-TE

240 mg BI 201335 once daily (QD) combined with PegIFN/RBV for 24 weeks, followed by an additional 24 weeks of PegIFN/RBV in treatment experienced (TE) patients

[PegIFN/RBV: PegIFN (180 µg/wk) and RBV (1000/1200mg/d)]

240 mg BID / LI-TE

240 mg BI 201335 twice daily (BID) combined with PegIFN/RBV for 24 weeks, with a 3-day lead-in phase of PegIFN/RBV (i.e. initiation of BI 201335 three days after first administration of PegIFN/RBV), followed by an additional 24 weeks of PegIFN/RBV in treatment experienced (TE) patients

[PegIFN/RBV: PegIFN (180 µg/wk) and RBV (1000/1200mg/d)]


Participant Flow:   Overall Study
    Placebo-TN     120 mg QD / LI-TN     240 mg QD / LI-TN     240 mg QD-TN     240 mg QD / LI-TE     240 mg QD-TE     240 mg BID / LI-TE  
STARTED     71     69     143     146     143     76     71  
COMPLETED     57     56     113     129     97     54     41  
NOT COMPLETED     14     13     30     17     46     22     30  
Adverse Event                 1                 3                 16                 8                 8                 3                 16  
Lack of Efficacy                 11                 4                 5                 3                 27                 15                 9  
Protocol Violation                 0                 1                 3                 1                 2                 1                 0  
Lost to Follow-up                 0                 1                 1                 1                 0                 1                 0  
Refused to continue trial medication                 1                 3                 2                 2                 6                 2                 3  
Not treated                 0                 0                 0                 0                 1                 0                 1  
Other than those stated above                 1                 1                 3                 2                 2                 0                 1  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Treated set: The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, whether randomised or not

Reporting Groups
  Description
Placebo-TN

Placebo once daily combined with PegIFN/RBV for 24 weeks, followed by an additional 24 weeks of PegIFN/RBV in treatment-naive (TN) patients

[PegIFN/RBV : PegIFN (180 µg/wk) and RBV (1000/1200mg/d)]

120 mg QD / LI-TN

120 mg BI 201335 (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 three days after first administration of PegIFN/RBV), followed by an additional 24 weeks of PegIFN/RBV in treatment naive (TN) patients

[PegIFN/RBV: PegIFN (180 µg/wk) and RBV (1000/1200mg/d)]

240 mg QD / LI-TN

240 mg BI 201335 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 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

[PegIFN/RBV: PegIFN (180 µg/wk) and RBV (1000/1200mg/d)]

240 mg QD-TN

240 mg BI 201335 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

[PegIFN/RBV: PegIFN (180 µg/wk) and RBV (1000/1200mg/d)]

240 mg QD / LI-TE

240 mg BI 201335 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 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

[PegIFN/RBV: PegIFN (180 µg/wk) and RBV (1000/1200mg/d)]

240 mg QD-TE

240 mg BI 201335 once daily (QD) combined with PegIFN/RBV for 24 weeks, followed by an additional 24 weeks of PegIFN/RBV in treatment experienced (TE) patients

[PegIFN/RBV: PegIFN (180 µg/wk) and RBV (1000/1200mg/d)]

240 mg BID / LI-TE

240 mg BI 201335 twice daily (BID) combined with PegIFN/RBV for 24 weeks, with a 3-day lead-in phase of PegIFN/RBV (i.e. initiation of BI 201335 three days after first administration of PegIFN/RBV), followed by an additional 24 weeks of PegIFN/RBV in treatment experienced (TE) patients

[PegIFN/RBV: PegIFN (180 µg/wk) and RBV (1000/1200mg/d)]

Total Total of all reporting groups

Baseline Measures
    Placebo-TN     120 mg QD / LI-TN     240 mg QD / LI-TN     240 mg QD-TN     240 mg QD / LI-TE     240 mg QD-TE     240 mg BID / LI-TE     Total  
Number of Participants  
[units: participants]
  71     69     143     146     142     76     70     717  
Age  
[units: years]
Mean (Standard Deviation)
  45.6  (10.86)     46.3  (10.92)     44.7  (10.18)     46.3  (10.48)     48.7  (9.58)     49.6  (8.42)     50.1  (8.34)     47.14  (9.91)  
Gender  
[units: participants]
               
Female     30     29     69     67     41     26     29     291  
Male     41     40     74     79     101     50     41     426  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Virological Response 4 Weeks After the End of Treatment With BI 201335 or Placebo   [ Time Frame: Week 28 ]

2.  Primary:   Sustained Virological Response 24 Weeks (SVR24) After Completion of All Therapy   [ Time Frame: Day 155 after the end of all treatment ]

3.  Secondary:   Virological Response at Week 2   [ Time Frame: Week 2 ]

4.  Secondary:   Virological Response at Week 4   [ Time Frame: Week 4 ]

5.  Secondary:   Early Virological Response (EVR)   [ Time Frame: Baseline and Week 12 ]

6.  Secondary:   Extended Rapid Virological Response (eRVR)   [ Time Frame: Week 4 and Week 12 ]

7.  Secondary:   Complete Early Virological Response (cEVR)   [ Time Frame: Week 12 ]

8.  Secondary:   End of Treatment Response at Week 24   [ Time Frame: Week 24 ]

9.  Secondary:   End of Treatment Response at End of All Therapy   [ Time Frame: Week 24 or Week 48 ]

10.  Secondary:   Sustained Virological Response 12 Weeks (SVR12) After Completion of All Therapy   [ Time Frame: Week 36 or Week 60 ]

11.  Secondary:   Time to Reach a Plasma HCV RNA Level Below the Lower Limit of Detection   [ Time Frame: On or after day 155 post end of all treatment ]

12.  Secondary:   Time to Loss of Virological Response   [ Time Frame: Week 24 ]

13.  Secondary:   Virological Rebound   [ Time Frame: Week 24 or Week 48 ]

14.  Secondary:   Breakthrough on BI 201335/Placebo (Rebound While All 3 Treatments Were Still Ongoing)   [ Time Frame: Up to Week 24 ]

15.  Secondary:   Breakthrough on PegIFN/RBV (Rebound While Only PegIFN/RBV Treatment Alone Was Still Ongoing)   [ Time Frame: Week 24 through Week 48 ]

16.  Secondary:   Relapse   [ Time Frame: post-End of treatment (i.e. post 48 weeks) ]

17.  Secondary:   Change From Baseline to Week 24 in Diastolic Blood Pressure and Systolic Blood Pressure   [ Time Frame: Baseline and Week 24 ]

18.  Secondary:   Change From Baseline to Week 24 in Pulse Rate   [ Time Frame: Baseline and Week 24 ]

19.  Secondary:   Change From Baseline to Week 24 in Weight of the Patients   [ Time Frame: Baseline and Week 24 ]

20.  Secondary:   Global Assessment of Tolerability   [ Time Frame: Week 24 ]

21.  Secondary:   Change From Baseline to Week 24 in Haemoglobin of the Patients   [ Time Frame: Baseline and Week 24 ]

22.  Secondary:   Number of Patients [N(%)] With Transitions Relative to Reference Range for Laboratory Parameter Haemoglobin   [ Time Frame: Baseline and Week 24 ]

23.  Secondary:   Change From Baseline to Week 24 in Absolute Neutrophils of the Patients   [ Time Frame: Baseline and Week 24 ]

24.  Secondary:   Number of Patients [N(%)] With Transitions Relative to Reference Range for Laboratory Parameter Absolute Neutrophils   [ Time Frame: Baseline and Week 24 ]

25.  Secondary:   Change From Baseline to Week 24 in ALT/GPT,SGPT of the Patients   [ Time Frame: Baseline and Week 24 ]

26.  Secondary:   Number of Patients [N(%)] With Transitions Relative to Reference Range for Laboratory Parameter ALT/GPT,SGPT   [ Time Frame: Baseline and Week 24 ]

27.  Secondary:   Change From Baseline to Week 24 in Total Bilirubin of the Patients   [ Time Frame: Baseline and Week 24 ]

28.  Secondary:   Number of Patients [N(%)] With Transitions Relative to Reference Range for Laboratory Parameter Total Bilirubin   [ Time Frame: Baseline and Week 24 ]

29.  Secondary:   Trough Concentration (Cpre,ss) of Faldaprevir at Steady State   [ Time Frame: Week 8, week 10, week 12, week 24 ]

30.  Secondary:   Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1000 mg/Day RBV)   [ Time Frame: Week 8, week 10, week 12, week 24 ]

31.  Secondary:   Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1200 mg/Day RBV)   [ Time Frame: Week 8, week 10, week 12, week 24 ]

32.  Secondary:   Trough Concentration (Cpre,ss) of PegIFN at Steady State   [ Time Frame: Week 8, week 10, week 12, week 24 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Boehringer Ingelheim Call Center
Organization: Boehringer Ingelheim
phone: 1-800-243-0127
e-mail: clintriage.rdg@boehringer-ingelheim.com



Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT00774397     History of Changes
Other Study ID Numbers: 1220.5
2008-003538-11 ( EudraCT Number: EudraCT )
Study First Received: October 16, 2008
Results First Received: July 3, 2015
Last Updated: October 14, 2015
Health Authority: Argentina: A.N.M.A.T. (Administracion Nacional de Medicamentos, Alimentos y Tecnología Médica).
Australia: Dept of Health and Ageing Therapeutic Goods Admin
Austria: Federal Office for Safety in Health Care
Canada: Health Canada - Therapeutic Products Directorate
Czech Republic: State Institute for Drug Control (SUKL), CZ-100 41 Prague 10
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: BfArM (Bundesagentur für Arzneimittel und Medizinalproduke)
Korea, Republic of: Korea Food and Drug Administration
Netherlands: Central Committee on Research Involving Human Subjects (CCMO)
Portugal: National Pharmacy and Medicines Institute
Romania: National Medicines Agency, Bucharest
Spain: Spanish Agency for Medicines and Health Products
Switzerland: Swissmedic
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration