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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00947349
First received: July 21, 2009
Last updated: July 3, 2015
Last verified: July 2015
  Purpose

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 Intervention 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
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
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

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Number of Participants With Investigator Defined Drug-related Adverse Events in Triple Combination Therapy [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    Drug-related AEs were defined as those whose causal relationship with any one of the investigational products was considered by the investigator.

  • Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    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.

  • Assessment of Tolerability in Triple Combination Therapy [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    An assessment of tolerability for the safety of the triple combination therapy with BI 201335 NA, PegIFN α -2a and RBV.


Secondary Outcome Measures:
  • Week 2 Virological Response (W2VR) [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
    Number of patients satisfying W2VR (plasma HCV RNA (Hepatitis C Virus Ribonucleic acid) level below the limit of quantification (BLQ))

  • Week 4 Virological Response (W4VR) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    Number of patients satisfying W4VR (plasma HCV RNA level below the limit of quantification (BLQ))

  • Rapid Virological Response (RVR) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    Number of patients satisfying RVR (plasma HCV RNA level below the limit of detection (BLD) at Week 4)

  • Change From Baseline in HCV Viral Load [ Time Frame: baseline and week 4 ] [ Designated as safety issue: No ]
    Change form baseline in HCV viral load (log10) after 4 weeks

  • Day 28 Virologic Response [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    Number of patients with HCV viral load reduction >= 2 log10 at Week 4

  • Early Virological Response (EVR) [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
    Number of patients with reduction >= 2 log10 in plasma HCV RNA level at Week 12

  • Complete Early Virological Response (cEVR) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Number of patients with plasma HCV RNA level BLD at Week 12

  • End of Treatment Response (ETR) [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    Number of patients with plasma HCV RNA level BLD at week 48

  • Sustained Virologic Response (SVR) [ Time Frame: 72 weeks ] [ Designated as safety issue: No ]
    Number of patients with plasma HCV RNA level BLD 24 weeks after treatment completion

  • 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 ] [ Designated as safety issue: No ]
    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.

  • Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Standard of Care (SOC) With PegIFN α-2a and RBV [ Time Frame: 44 weeks ] [ Designated as safety issue: No ]
    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.

  • Assessment of Tolerability in Standard of Care (SOC) With PegIFN α -2a and RBV [ Time Frame: 44 weeks ] [ Designated as safety issue: No ]
    An assessment of tolerability for the safety of the SOC with PegIFN alfa-2a and RBV.

  • 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 ] [ Designated as safety issue: No ]
    Area under the curve (AUC) concentration after the first dose of BI 201335 ZW

  • 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 ] [ Designated as safety issue: No ]
    Maximum concentration of BI 201335 ZW after multiple oral admin. of BI 201335 NA with RBV and PegIFN alfa-2a

  • 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 ] [ Designated as safety issue: No ]
    AUC at steady state after 4 weeks combination of the last dose

  • 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 ] [ Designated as safety issue: No ]
    Maximum concentration of BI 201335 ZW at steady state

  • 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 ] [ Designated as safety issue: No ]
    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

  • Cmax of RBV [ Time Frame: -0:10, 1,2,3,4,5,6,8,10,11:50, 23:50 hours on the first dose ] [ Designated as safety issue: No ]
    Maximum Plasma concentration of RBV after multiple oral admin. of placebo with RBV and PegIFN alfa-2a

  • 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 ] [ Designated as safety issue: No ]
    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

  • 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 ] [ Designated as safety issue: No ]
    Maximum Plasma concentration of RBV after multiple oral admin. of BI 201335 NA (or placebo) with RBV and PegIFN alfa-2a at steady state

  • 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 ] [ Designated as safety issue: No ]
    Time to maximum plasma concentration (tmax) of BI 201335 ZW after the first dose of BI 201335 NA with RBV and PegIFN alfa-2a

  • 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 ] [ Designated as safety issue: No ]
    Time to maximum plasma concentration (tmax) of RBV after the first dose of BI 201335 NA with RBV and PegIFN alfa-2a

  • 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 ] [ Designated as safety issue: No ]
    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

  • 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 ] [ Designated as safety issue: No ]
    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

  • 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 ] [ Designated as safety issue: No ]
    terminal half-life of the analyte in plasma at steady state (t1/2,ss)

  • 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 ] [ Designated as safety issue: No ]
    Minimum concentration of the analyte (BI 201335 ZW) in plasma over the dosing interval at steady state

  • 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 ] [ Designated as safety issue: No ]
    Minimum concentration of the analyte (RBV) in plasma over the dosing interval at steady state

  • 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 ] [ Designated as safety issue: No ]
    average plasma concentration (Cavg) of BI 201335 ZW

  • 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 ] [ Designated as safety issue: No ]
    average plasma concentration (Cavg) of RBV

  • 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 ] [ Designated as safety issue: No ]
    apparent clearance of the analyte (BI 201335 ZW) in plasma at steady state (CL/F,ss) following multiple oral administration


Enrollment: 22
Study Start Date: July 2009
Study Completion Date: August 2011
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   20 Years to 70 Years
Genders Eligible for Study:   Both
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: 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
  More Information

Additional Information:
No publications provided

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT00947349     History of Changes
Other Study ID Numbers: 1220.14
Study First Received: July 21, 2009
Results First Received: January 22, 2015
Last Updated: July 3, 2015
Health Authority: Japan: Pharmaceuticals and Medical Devices Agency

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

ClinicalTrials.gov processed this record on July 30, 2015