Safety, Antiviral Effect and PK of BI 207127 + BI 201335 +/- RBV for 4 up to 40 Weeks in Patients With Chronic HCV Genotype 1 Infection

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01132313
First received: May 3, 2010
Last updated: December 22, 2015
Last verified: December 2015
Results First Received: October 29, 2015  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Hepatitis C, Chronic
Interventions: Drug: BI 207127
Drug: BI 201335
Drug: Ribavirin
Drug: BI 207217

  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
This trial was conducted in 4 parts, each consisting of randomised, open-label treatments.

Reporting Groups
  Description
Part 1: 400mg DBV and 120mg FDV - 4w Part 1: 4 weeks of 400mg Deleobuvir tablet TID and 120mg Faldaprevir soft gelatin capsule QD in combination with RBV tablet. From week 5 to week 24, patients received treatment with FDV 120mg QD in combination with standard of care (SOC) PegIFN/RBV (triple therapy period)
Part 1: 600mg DBV and 120mg FDV - 4w Part 1: 4 weeks of 600mg Deleobuvir (DBV, BI 207127) tablet three times per day (TID) and 120mg Faldaprevir (FDV, BI 201335) soft gelatin capsule once daily (QD) in combination with Ribavirin (RBV) tablet. From week 5 to week 24, patients received treatment with FDV 120mg QD in combination with SOC PegIFN/RBV (triple therapy period)
Part 2: 600mg DBV and 120mg FDV - 16w Part 2: 16 weeks of 600mg Deleobuvir tablet TID and 120mg Faldaprevir soft gelatin capsule QD in combination with RBV tablet. Patients who discontinued their assigned treatment early due to lack of antiviral activity could receive additional treatment with PegIFN/RBV for up to 24 weeks.
Part 2: 600mg DBV TID and 120mg FDV - 28w Part 2: 28 weeks of 600mg Deleobuvir tablet TID and 120mg Faldaprevir soft gelatin capsule QD in combination with RBV tablet. Patients who discontinued their assigned treatment early due to lack of antiviral activity could receive additional treatment with PegIFN/RBV for up to 24 weeks.
Part 2: 600mg DBV and 120mg FDV - 40w Part 2: 40 weeks of 600mg Deleobuvir tablet TID and 120mg Faldaprevir soft gelatin capsule QD in combination with RBV tablet. Patients who discontinued their assigned treatment early due to lack of antiviral activity could receive additional treatment with PegIFN/RBV for up to 24 weeks.
Part 2: 600mg DBV BID and 120mg FDV - 28w Part 2: 28 weeks of 600mg Deleobuvir tablet twice a day (BID) and 120mg Faldaprevir soft gelatin capsule QD in combination with RBV tablet. Patients who discontinued their assigned treatment early due to lack of antiviral activity could receive additional treatment with PegIFN/RBV for up to 24 weeks.
Part 2: 600mg DBV and 120mg FDV, no RBV - 28w Part 2: 28 weeks of 600mg Deleobuvir tablet TID and 120mg Faldaprevir soft gelatin capsule QD, without RBV. Patients who discontinued their assigned treatment early due to lack of antiviral activity could receive additional treatment with PegIFN/RBV for up to 24 weeks.
Part 3: 600mg DBV and 120mg FDV - 16w Part 3: 16 weeks of 600mg Deleobuvir tablet BID and 120mg Faldaprevir soft gelatin capsule QD in combination with RBV tablet. Patients who discontinued their assigned treatment early due to lack of antiviral activity could receive additional treatment with PegIFN/RBV for up to 24 weeks.
Part 3: 800mg DBV and 120mg FDV - 24w Part 3: 24 weeks of 800mg Deleobuvir tablet BID and 120mg Faldaprevir soft gelatin capsule QD in combination with RBV tablet. Patients who discontinued their assigned treatment early due to lack of antiviral activity could receive additional treatment with PegIFN/RBV for up to 24 weeks.
Part 3: 600mg DBV and 120mg FDV - 24w Part 3: 24 weeks of 600mg Deleobuvir tablet TID and 120mg Faldaprevir soft gelatin capsule QD in combination with RBV tablet. Patients who discontinued their assigned treatment early due to lack of antiviral activity could receive additional treatment with PegIFN/RBV for up to 24 weeks.
Part 4: 600 mg DBV and 120mg FDV - 16w Part 4: 16 weeks of 600mg Deleobuvir tablet BID and 120mg Faldaprevir soft gelatin capsule QD in combination with RBV tablet.
Part 4: 600 mg DBV and 120mg FDV - 24w Part 4: 24 weeks of 600mg Deleobuvir tablet BID and 120mg Faldaprevir soft gelatin capsule QD in combination with RBV tablet.

Participant Flow:   Overall Study
    Part 1: 400mg DBV and 120mg FDV - 4w     Part 1: 600mg DBV and 120mg FDV - 4w     Part 2: 600mg DBV and 120mg FDV - 16w     Part 2: 600mg DBV TID and 120mg FDV - 28w     Part 2: 600mg DBV and 120mg FDV - 40w     Part 2: 600mg DBV BID and 120mg FDV - 28w     Part 2: 600mg DBV and 120mg FDV, no RBV - 28w     Part 3: 600mg DBV and 120mg FDV - 16w     Part 3: 800mg DBV and 120mg FDV - 24w     Part 3: 600mg DBV and 120mg FDV - 24w     Part 4: 600 mg DBV and 120mg FDV - 16w     Part 4: 600 mg DBV and 120mg FDV - 24w  
STARTED     17     17     81     80     79     79     49     32     26     25     1     2  
COMPLETED     14     17     61     48     34     54     19     24     5     5     0     2  
NOT COMPLETED     3     0     20     32     45     25     30     8     21     20     1     0  
Lack of Efficacy                 1                 0                 0                 0                 0                 0                 0                 3                 14                 16                 0                 0  
Not treated                 2                 0                 0                 0                 2                 1                 3                 0                 0                 0                 0                 0  
Adverse Event                 0                 0                 4                 10                 19                 6                 5                 3                 7                 2                 0                 0  
Protocol Violation                 0                 0                 0                 1                 0                 0                 0                 0                 0                 0                 0                 0  
Lost to Follow-up                 0                 0                 1                 0                 0                 0                 0                 1                 0                 0                 0                 0  
Withdrawal by Subject                 0                 0                 3                 3                 6                 0                 1                 0                 0                 2                 0                 0  
Lack of antiviral response                 0                 0                 12                 18                 18                 18                 21                 0                 0                 0                 1                 0  
Other reason not defined above                 0                 0                 0                 0                 0                 0                 0                 1                 0                 0                 0                 0  



  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 which included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment regardless of randomisation.

Reporting Groups
  Description
Part 1: 400mg DBV and 120mg FDV - 4w Part 1: 4 weeks of 400mg Deleobuvir tablet TID and 120mg Faldaprevir soft gelatin capsule QD in combination with RBV tablet. From week 5 to week 24, patients received treatment with FDV 120mg QD in combination with standard of care (SOC) PegIFN/RBV (triple therapy period)
Part 1: 600mg DBV and 120mg FDV - 4w Part 1: 4 weeks of 600mg Deleobuvir (DBV, BI 207127) tablet three times per day (TID) and 120mg Faldaprevir (FDV, BI 201335) soft gelatin capsule once daily (QD) in combination with Ribavirin (RBV) tablet. From week 5 to week 24, patients received treatment with FDV 120mg QD in combination with SOC PegIFN/RBV (triple therapy period)
Part 2: 600mg DBV and 120mg FDV - 16w Part 2: 16 weeks of 600mg Deleobuvir tablet TID and 120mg Faldaprevir soft gelatin capsule QD in combination with RBV tablet. Patients who discontinued their assigned treatment early due to lack of antiviral activity could receive additional treatment with PegIFN/RBV for up to 24 weeks.
Part 2: 600mg DBV TID and 120mg FDV - 28w Part 2: 28 weeks of 600mg Deleobuvir tablet TID and 120mg Faldaprevir soft gelatin capsule QD in combination with RBV tablet. Patients who discontinued their assigned treatment early due to lack of antiviral activity could receive additional treatment with PegIFN/RBV for up to 24 weeks.
Part 2: 600mg DBV and 120mg FDV - 40w Part 2: 40 weeks of 600mg Deleobuvir tablet TID and 120mg Faldaprevir soft gelatin capsule QD in combination with RBV tablet. Patients who discontinued their assigned treatment early due to lack of antiviral activity could receive additional treatment with PegIFN/RBV for up to 24 weeks.
Part 2: 600mg DBV BID and 120mg FDV - 28w Part 2: 28 weeks of 600mg Deleobuvir tablet twice a day (BID) and 120mg Faldaprevir soft gelatin capsule QD in combination with RBV tablet. Patients who discontinued their assigned treatment early due to lack of antiviral activity could receive additional treatment with PegIFN/RBV for up to 24 weeks.
Part 2: 600mg DBV and 120mg FDV, no RBV - 28w Part 2: 28 weeks of 600mg Deleobuvir tablet TID and 120mg Faldaprevir soft gelatin capsule QD, without RBV. Patients who discontinued their assigned treatment early due to lack of antiviral activity could receive additional treatment with PegIFN/RBV for up to 24 weeks.
Part 3: 600mg DBV and 120mg FDV - 16w Part 3: 16 weeks of 600mg Deleobuvir tablet BID and 120mg Faldaprevir soft gelatin capsule QD in combination with RBV tablet. Patients who discontinued their assigned treatment early due to lack of antiviral activity could receive additional treatment with PegIFN/RBV for up to 24 weeks.
Part 3: 800mg DBV and 120mg FDV - 24w Part 3: 24 weeks of 800mg Deleobuvir tablet BID and 120mg Faldaprevir soft gelatin capsule QD in combination with RBV tablet. Patients who discontinued their assigned treatment early due to lack of antiviral activity could receive additional treatment with PegIFN/RBV for up to 24 weeks.
Part 3: 600mg DBV and 120mg FDV - 24w Part 3: 24 weeks of 600mg Deleobuvir tablet TID and 120mg Faldaprevir soft gelatin capsule QD in combination with RBV tablet. Patients who discontinued their assigned treatment early due to lack of antiviral activity could receive additional treatment with PegIFN/RBV for up to 24 weeks.
Part 4: 600 mg DBV and 120mg FDV - 16w Part 4: 16 weeks of 600mg Deleobuvir tablet BID and 120mg Faldaprevir soft gelatin capsule QD in combination with RBV tablet.
Part 4: 600 mg DBV and 120mg FDV - 24w Part 4: 24 weeks of 600mg Deleobuvir tablet BID and 120mg Faldaprevir soft gelatin capsule QD in combination with RBV tablet.
Total Total of all reporting groups

Baseline Measures
    Part 1: 400mg DBV and 120mg FDV - 4w     Part 1: 600mg DBV and 120mg FDV - 4w     Part 2: 600mg DBV and 120mg FDV - 16w     Part 2: 600mg DBV TID and 120mg FDV - 28w     Part 2: 600mg DBV and 120mg FDV - 40w     Part 2: 600mg DBV BID and 120mg FDV - 28w     Part 2: 600mg DBV and 120mg FDV, no RBV - 28w     Part 3: 600mg DBV and 120mg FDV - 16w     Part 3: 800mg DBV and 120mg FDV - 24w     Part 3: 600mg DBV and 120mg FDV - 24w     Part 4: 600 mg DBV and 120mg FDV - 16w     Part 4: 600 mg DBV and 120mg FDV - 24w     Total  
Number of Participants  
[units: participants]
  15     17     81     80     77     78     46     32     26     25     1     2     480  
Age  
[units: Years]
Mean (Standard Deviation)
  50.8  (10.0)     50.8  (11.5)     48.6  (11.3)     47.3  (11.2)     48.9  (10.7)     47.9  (11.1)     45.3  (13.0)     48.9  (11.8)     47.2  (13.4)     46.5  (12.5)     59.0 [1]   52.5  (4.9)     48.1  (11.4)  
Gender  
[units: Participants]
                         
Female     7     7     36     39     41     37     22     20     11     11     1     2     234  
Male     8     10     45     41     36     41     24     12     15     14     0     0     246  
[1] Not calculable due to only one patient in treatment group



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Part 1: Rapid Virological Response (RVR)   [ Time Frame: 4 weeks ]

2.  Primary:   Part 2: Sustained Virological Response (SVR)   [ Time Frame: From drug administration until 12 weeks after end of treatment, up to 52 weeks ]

3.  Primary:   Part 3 and 4: Sustained Virological Response (SVR)   [ Time Frame: From drug administration until 12 weeks after end of treatment, up to 36 weeks ]

4.  Secondary:   Part 1: Time to Virological Response   [ Time Frame: From drug administration until end of drug administration, up to 4 weeks ]

5.  Secondary:   Part 2: Time to Virological Response   [ Time Frame: From drug administration until end of drug administration, up to 40 weeks ]

6.  Secondary:   Part 1 and 2: Plasma HCV RNA Level Not Detectable at Week 4   [ Time Frame: 4 weeks ]

7.  Secondary:   Part 2: Sustained Virological Response at 4 and 24 Weeks After End of Treatment   [ Time Frame: 4 weeks and 24 weeks after the end of treatment, up to 64 weeks ]

8.  Secondary:   Part 3 and 4: Plasma HCV RNA Level <25 IU/mL at Week 4 and 12 of Treatment   [ Time Frame: Week 4 and 12 ]

9.  Secondary:   Part 3 and 4: Sustained Virological Response (SVR) at 4 Weeks After End of Treatment   [ Time Frame: up to 28 weeks ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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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
There were only 3 patients entered in part 4 of the trial, therefore no formal analyses of efficacy data were performed.


  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


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01132313     History of Changes
Other Study ID Numbers: 1241.21
2009-018197-66 ( EudraCT Number: EudraCT )
Study First Received: May 3, 2010
Results First Received: October 29, 2015
Last Updated: December 22, 2015
Health Authority: Australia: Dept of Health and Ageing Therapeutic Goods Admin
Austria: Medicines and Medical Devices Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
New Zealand: Medsafe
Portugal: National Pharmacy and Medicines Institute
Romania: National Medicines Agency
Spain: Spanish Agency of Medicines
Switzerland: Swissmedic
United States: Food and Drug Administration