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Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Rising Oral Doses of BI 201335 as Softgel Capsule in Naive Hepatitis C Virus (HCV) Patients

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ClinicalTrials.gov Identifier: NCT00947349
Recruitment Status : Completed
First Posted : July 28, 2009
Results First Posted : July 7, 2015
Last Update Posted : July 7, 2015
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Brief Summary:

The current Standard of Care (SOC) for chronic HCV infection, which is pegylated interferon-alfa as combination therapy with ribavirin for 24-48 weeks of treatment, is effective in only part of the patients and is often associated with severe adverse effects leading to discontinuation of treatment and dose modifications.

A number of compounds with direct activity are currently under clinical development, incl. BI 201335. BI 201335 works by preventing the Hepatitis C virus from replicating by binding to the HCV protease (enzyme). The main purpose of this clinical trial with BI 201335 is to see how well BI 201335 works and how safe BI 201335 is to use daily in combination with PegIFN and RBV in HCV infected patients


Condition or disease Intervention/treatment Phase
Hepatitis C Pharmacokinetics Drug: ribavirin (RBV) Drug: pegylated interferon (PegIFN) alfa-2a Drug: BI 201335 NA low placebo Drug: BI 201335 NA high Drug: BI 201335 NA low Drug: BI 201335 NA high placebo Drug: Placebo Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 22 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Primary Purpose: Treatment
Official Title: Safety, Pharmacokinetics and Antiviral Effect of BI 201335 NA in HCV-1 Infected Patients Treated for 28 Days for Treatment naïve and Experienced Patients Treated in Combination With Peg Interferon Alfa-2a and Ribavirin
Study Start Date : July 2009
Actual Primary Completion Date : August 2011
Actual Study Completion Date : August 2011

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: BI 201335 NA low TN
patient to receive a capsule containing low dose of BI 201335 NA/Drug for treatment-naive (TN) patients
Drug: pegylated interferon (PegIFN) alfa-2a
pegylated interferon (PegIFN) alfa-2a

Drug: BI 201335 NA low placebo
Placebo

Drug: ribavirin (RBV)
ribavirin (RBV)

Drug: BI 201335 NA low
BI 201335 NA

Experimental: BI 201335 NA high TN
patient to receive a capsule containing high dose of BI 201335 NA/Drug for treatment-naive (TN )patients
Drug: ribavirin (RBV)
ribavirin (RBV)

Drug: pegylated interferon (PegIFN) alfa-2a
pegylated interferon (PegIFN) alfa-2a

Drug: BI 201335 NA high
BI 201335 NA high

Drug: BI 201335 NA high placebo
placebo

Experimental: BI 201335 NA high TE
patient to receive a capsule containing high dose of BI 201335 NA/Drug for treatment-experienced (TE) patients
Drug: pegylated interferon (PegIFN) alfa-2a
pegylated interferon (PegIFN) alfa-2a

Drug: ribavirin (RBV)
ribavirin (RBV)

Drug: BI 201335 NA high
BI 201335 NA high

Placebo Comparator: Placebo in Treatment Naive (TN) Patients Drug: Placebo



Primary Outcome Measures :
  1. Number of Participants With Investigator Defined Drug-related Adverse Events in Triple Combination Therapy [ Time Frame: 4 weeks ]
    Drug-related AEs were defined as those whose causal relationship with any one of the investigational products was considered by the investigator.

  2. Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy [ Time Frame: 4 weeks ]
    Frequency of patients with possible clinically significant abnormalities or clinically significant laboratory test value changes over time in triple combination therapy for treatment naive patients and treatment experienced patients.

  3. Assessment of Tolerability in Triple Combination Therapy [ Time Frame: 4 weeks ]
    An assessment of tolerability for the safety of the triple combination therapy with BI 201335 NA, PegIFN α -2a and RBV.


Secondary Outcome Measures :
  1. Week 2 Virological Response (W2VR) [ Time Frame: 2 weeks ]
    Number of patients satisfying W2VR (plasma HCV RNA (Hepatitis C Virus Ribonucleic acid) level below the limit of quantification (BLQ))

  2. Week 4 Virological Response (W4VR) [ Time Frame: 4 weeks ]
    Number of patients satisfying W4VR (plasma HCV RNA level below the limit of quantification (BLQ))

  3. Rapid Virological Response (RVR) [ Time Frame: 4 weeks ]
    Number of patients satisfying RVR (plasma HCV RNA level below the limit of detection (BLD) at Week 4)

  4. Change From Baseline in HCV Viral Load [ Time Frame: baseline and week 4 ]
    Change form baseline in HCV viral load (log10) after 4 weeks

  5. Day 28 Virologic Response [ Time Frame: 4 weeks ]
    Number of patients with HCV viral load reduction >= 2 log10 at Week 4

  6. Early Virological Response (EVR) [ Time Frame: 12 Weeks ]
    Number of patients with reduction >= 2 log10 in plasma HCV RNA level at Week 12

  7. Complete Early Virological Response (cEVR) [ Time Frame: 12 weeks ]
    Number of patients with plasma HCV RNA level BLD at Week 12

  8. End of Treatment Response (ETR) [ Time Frame: 48 weeks ]
    Number of patients with plasma HCV RNA level BLD at week 48

  9. Sustained Virologic Response (SVR) [ Time Frame: 72 weeks ]
    Number of patients with plasma HCV RNA level BLD 24 weeks after treatment completion

  10. Number of Participants With Investigator Defined Drug-related Adverse Events in Standard of Care (SOC) With PegIFN α-2a and RBV [ Time Frame: 44 weeks ]
    Drug-related AEs in SOC treatment period were defined as those whose causal relationship with any one of the investigational products was considered by the investigator.

  11. Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Standard of Care (SOC) With PegIFN α-2a and RBV [ Time Frame: 44 weeks ]
    Frequency of patients with possible clinically significant abnormalities or clinically significant laboratory test value changes over time in SOC period for treatment naive patients and treatment experienced patients.

  12. Assessment of Tolerability in Standard of Care (SOC) With PegIFN α -2a and RBV [ Time Frame: 44 weeks ]
    An assessment of tolerability for the safety of the SOC with PegIFN alfa-2a and RBV.

  13. AUCτ,1 for BI 201335 ZW [ Time Frame: 10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the first dose ]
    Area under the curve (AUC) concentration after the first dose of BI 201335 ZW

  14. Cmax of BI 201335 ZW [ Time Frame: 10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the first dose ]
    Maximum concentration of BI 201335 ZW after multiple oral admin. of BI 201335 NA with RBV and PegIFN alfa-2a

  15. AUCτ,ss of BI 201335 ZW [ Time Frame: 10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the last dose ]
    AUC at steady state after 4 weeks combination of the last dose

  16. Cmax,ss of BI 201335 ZW [ Time Frame: 10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the last dose ]
    Maximum concentration of BI 201335 ZW at steady state

  17. AUCτ,1 for Ribavirin (RBV) [ Time Frame: -0:10, 1,2,3,4,5,6,8,10,11:50, 23:50 hours on the first dose ]
    Area under the plasma concentration curve of RBV after the first dose of placebo or BI 201335 NA with with RBV and PegIFN alfa-2a

  18. Cmax of RBV [ Time Frame: -0:10, 1,2,3,4,5,6,8,10,11:50, 23:50 hours on the first dose ]
    Maximum Plasma concentration of RBV after multiple oral admin. of placebo with RBV and PegIFN alfa-2a

  19. AUCτ,ss of RBV [ Time Frame: -0:10, 1,2,3,4,5,6,8,10,11:50, 23:50 hours on the last dose ]
    Area under the plasma concentration curve of RBV after the multiple oral administration of BI 201335 NA (or placebo) with RBV and PegIFN alfa-2a at steady state

  20. Cmax,ss of RBV [ Time Frame: -0:10, 1,2,3,4,5,6,8,10,11:50, 23:50 hours on the last dose ]
    Maximum Plasma concentration of RBV after multiple oral admin. of BI 201335 NA (or placebo) with RBV and PegIFN alfa-2a at steady state

  21. Tmax for BI 201335 ZW [ Time Frame: 10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the first dose ]
    Time to maximum plasma concentration (tmax) of BI 201335 ZW after the first dose of BI 201335 NA with RBV and PegIFN alfa-2a

  22. Tmax for RBV [ Time Frame: 10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the first dose ]
    Time to maximum plasma concentration (tmax) of RBV after the first dose of BI 201335 NA with RBV and PegIFN alfa-2a

  23. Tmax, ss for BI 201335 ZW [ Time Frame: 10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the last dose ]
    Time from last dosing to the maximum plasma concentration (tmax) of BI 201335 ZW after the last dose of BI 201335 NA with RBV and PegIFN alfa-2a at steady state

  24. Tmax, ss for RBV [ Time Frame: 10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the last dose ]
    Time to the maximum plasma concentration (tmax) of RBV after the last dose of BI 201335 NA with RBV and PegIFN alfa-2a at steady state

  25. t1/2,ss for BI 201335 ZW [ Time Frame: 10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the last dose ]
    terminal half-life of the analyte in plasma at steady state (t1/2,ss)

  26. Cmin,ss for BI 201335 ZW [ Time Frame: 10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the last dose ]
    Minimum concentration of the analyte (BI 201335 ZW) in plasma over the dosing interval at steady state

  27. Cmin,ss for RBV [ Time Frame: 10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the last dose ]
    Minimum concentration of the analyte (RBV) in plasma over the dosing interval at steady state

  28. Cavg for BI 201335 ZW [ Time Frame: 10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the last dose ]
    average plasma concentration (Cavg) of BI 201335 ZW

  29. Cavg for RBV [ Time Frame: 10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the last dose ]
    average plasma concentration (Cavg) of RBV

  30. CL/F,ss for BI 201335 ZW [ Time Frame: 10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the last dose ]
    apparent clearance of the analyte (BI 201335 ZW) in plasma at steady state (CL/F,ss) following multiple oral administration



Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • chronic HCV genotype-1;
  • high viral load

Exclusion criteria:

  • Mixed genotype (1/2, 1/3, or 1/4), diagnosed by genotypic testing at screening
  • Previous treatment with protease inhibitor

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00947349


Locations
Japan
1220.14.003 Boehringer Ingelheim Investigational Site
Kurashiki, Okayama, Japan
1220.14.001 Boehringer Ingelheim Investigational Site
Minato-ku, Tokyo, Japan
1220.14.002 Boehringer Ingelheim Investigational Site
Nishinomiya, Hyogo, Japan
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim

Additional Information:
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT00947349     History of Changes
Other Study ID Numbers: 1220.14
First Posted: July 28, 2009    Key Record Dates
Results First Posted: July 7, 2015
Last Update Posted: July 7, 2015
Last Verified: July 2015

Additional relevant MeSH terms:
Hepatitis
Hepatitis C
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Flaviviridae Infections
RNA Virus Infections
Interferons
Ribavirin
Peginterferon alfa-2a
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action