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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

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

July 21, 2009
July 3, 2015
July 2009
August 2011   (final data collection date for primary outcome measure)
  • 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.
There is no primary endpoint of efficacy in this trial. Instead, safety for the triple combination therapy will be assessed based on: 1. Adverse Events 2. Laboratory test abnormalities 3. Laboratory test value changes over time 4. Tolerability [ Time Frame: 4 weeks ]
Complete list of historical versions of study NCT00947349 on ClinicalTrials.gov Archive Site
  • 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
Loss of virological response at week 4, 12, 24, 48 and 72 [ Time Frame: 72 weeks ]
Not Provided
Not Provided
 
Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Rising Oral Doses of BI 201335 as Softgel Capsule in Naive Hepatitis C Virus (HCV) Patients
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

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

Not Provided
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
  • Hepatitis C
  • Pharmacokinetics
  • Drug: ribavirin (RBV)
    ribavirin (RBV)
  • Drug: pegylated interferon (PegIFN) alfa-2a
    pegylated interferon (PegIFN) alfa-2a
  • Drug: BI 201335 NA low placebo
    Placebo
  • Drug: BI 201335 NA high
    BI 201335 NA high
  • Drug: BI 201335 NA low
    BI 201335 NA
  • Drug: BI 201335 NA high placebo
    placebo
  • Drug: Placebo
  • Experimental: BI 201335 NA low TN
    patient to receive a capsule containing low dose of BI 201335 NA/Drug for treatment-naive (TN) patients
    Interventions:
    • Drug: pegylated interferon (PegIFN) alfa-2a
    • Drug: BI 201335 NA low placebo
    • Drug: ribavirin (RBV)
    • Drug: BI 201335 NA low
  • Experimental: BI 201335 NA high TN
    patient to receive a capsule containing high dose of BI 201335 NA/Drug for treatment-naive (TN )patients
    Interventions:
    • Drug: ribavirin (RBV)
    • Drug: pegylated interferon (PegIFN) alfa-2a
    • Drug: BI 201335 NA high
    • Drug: BI 201335 NA high 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
    Interventions:
    • Drug: pegylated interferon (PegIFN) alfa-2a
    • Drug: ribavirin (RBV)
    • Drug: BI 201335 NA high
  • Placebo Comparator: Placebo in Treatment Naive (TN) Patients
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
22
August 2011
August 2011   (final data collection date for primary outcome measure)

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
Both
20 Years to 70 Years   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
Japan
 
NCT00947349
1220.14
Not Provided
Not Provided
Not Provided
Boehringer Ingelheim
Boehringer Ingelheim
Not Provided
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
Boehringer Ingelheim
July 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP