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: July 10, 2014
Last verified: July 2014

October 16, 2008
July 10, 2014
October 2008
November 2011   (final data collection date for primary outcome measure)
  • Sustained virological response 24 weeks after completion of therapy (SVR 24) weeks [ Time Frame: up to 72 weeks ] [ Designated as safety issue: No ]
  • Virological response of BI 201335 NA or placebo plus 4 weeks [ Time Frame: up to 28 weeks ] [ Designated as safety issue: No ]
  • Intensity of adverse events [ Time Frame: up to week 120 ] [ Designated as safety issue: No ]
  • Changes in vital signs (blood pressure, pulse rate) [ Time Frame: up to week 48 ] [ Designated as safety issue: No ]
  • Clinically relevant laboratory abnormalities [ Time Frame: up to week 48 ] [ Designated as safety issue: No ]
  • Laboratory test value changes over time [ Time Frame: up to week 48 ] [ Designated as safety issue: No ]
  • Tolerability assessment by investigator (good, satisfactory, not satisfactory, bad) [ Time Frame: up to week 48 ] [ Designated as safety issue: No ]
SVR
Complete list of historical versions of study NCT00774397 on ClinicalTrials.gov Archive Site
  • complete early virological response [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
  • Extended Rapid Virological Response (eRVR) [ Time Frame: Week 4 and Week 12 ] [ Designated as safety issue: No ]
  • End of treatment response [ Time Frame: Week 24, 48, 72 ] [ Designated as safety issue: No ]
  • sustained virological response at 12 weeks after completion of all therapy [ Time Frame: Week 36 or 60 ] [ Designated as safety issue: No ]
  • time to reach a plasma HCV RNA level below the lower limit of detection [ Time Frame: n.a. ] [ Designated as safety issue: No ]
  • time to loss of virological response [ Time Frame: n.a. ] [ Designated as safety issue: No ]
  • Virological Response (plasma HCV RNA level below the lower limit of quantification) [ Time Frame: Week 2 and week 4 ] [ Designated as safety issue: No ]
  • Virological rebound [ Time Frame: up to week 120 ] [ Designated as safety issue: No ]
  • Trough plasma concentrations (Cmin,ss) for BI 201335 ZW, ribavirin, and pegylated interferon α-2a [ Time Frame: Week 0 to Week 36 ] [ Designated as safety issue: No ]
  • Cmax,ss for patients participating in the steady state PK-substudy [ Time Frame: Week 10 ] [ Designated as safety issue: No ]
  • tmax,ss for BI 201335 ZW and ribavirin for patients participating in the steady state PK-substudy [ Time Frame: Week 10 ] [ Designated as safety issue: No ]
  • Cmin,ss for patients participating in the steady state PK-substudy [ Time Frame: Week 10 ] [ Designated as safety issue: No ]
  • AUCτ,ss for patients participating in the steady state PK-substudy [ Time Frame: Week 10 ] [ Designated as safety issue: No ]
  • CL/F,ss for patients participating in the steady state PK-substudy [ Time Frame: Week 10 ] [ Designated as safety issue: No ]
  • Early virological response [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
W2VR, W4VR, EVR, cEVR, ETR1335, ETR1335+4, ETR+12, time to VL BLD, time to loss of virological response
Not Provided
Not Provided
 
Antiviral Effect, Safety, and Pharmacokinetics of BI201335 +PegIFN/RBV in HCV-GT1 (SILEN-C1&2)
Antiviral Effect, Safety and Pharmacokinetics of BI 201335 NA in Hepatitis C Virus Genotype 1 Infected Treatment-naïve and Treatment-experienced Patients for 24 Weeks as Combination Therapy With Pegylated Interferon-alpha 2a and Ribavirin (Double-blinded, Randomised, Placebo-controlled, Phase II)

The objective was to investigate the antiviral effect, safety, and pharmacokinetics of BI 201335, given as a soft gelatine capsule, in patients with hepatitis C virus (HCV) genotype 1 infection. Combination therapy of BI 201335 with pegylated interferon α-2a (PegIFN) and ribavirin (RBV), with or without a 3-day lead-in, was assessed in treatment-naïve (TN) and treatment experienced (TE) 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, Chronic
  • Drug: Arm 3 BI 201335 NA
    240mg BI 201335 NA once daily with a 3 days lead-in phase of PegIFN/RB, 24 weeks
  • Drug: Arm 3 PegIFN/RBV
    PegIFN (180 µg/wk) and RBV (1000/1200mg/d), 24 or 48 weeks
  • Drug: Arm 4 BI 201335 NA
    120mg BI 201335 NA once daily, for 24 weeks
  • Drug: Arm 4 PegIFN/RBV
    PegIFN (180 µg/wk) and RBV (1000/1200mg/d),48 weeks
  • Drug: Arm 5 BI 201335 NA
    240mg BI 201335 NA once daily, 24 weeks
  • Drug: Arm 5 PegIFN/RBV
    PegIFN (180 µg/wk) and RBV (1000/1200mg/d),48 weeks
  • Drug: Arm 6 BI 201335 NA
    240mg BI 201335 NA once daily, 24 weeks
  • Drug: Arm 6 PegIFN/RBV
    PegIFN (180 µg/wk) and RBV (1000/1200mg/d), 24 or 48 weeks
  • Drug: Arm 7 BI 201335 NA
    240mg BI 201335 NA twice, 24 weeks
  • Drug: Arm 7 PegIFN/RBV
    PegIFN (180 µg/wk) and RBV (1000/1200mg/d),48 weeks
  • Drug: Arm 1 PegIFN/RBV
    PegIFN (180 µg/wk) and RBV (1000/1200mg/d),48 weeks
  • Drug: Arm 2 BI 201335 NA
    240mg BI 201335 NA once daily, 24 weeks
  • Drug: Arm 2 PegIFN/RBV
    PegIFN (180 µg/wk) and RBV (1000/1200mg/d), 24 or 48 weeks
  • Experimental: 2. 240 mg QD
    240mg BI 201335 NA once daily combined with PegIFN/RBV for 24 or 48weeks, in treatment-naive patients
    Interventions:
    • Drug: Arm 2 BI 201335 NA
    • Drug: Arm 2 PegIFN/RBV
  • Experimental: 3. 240 mg QD / LI
    240mg BI 201335 NA once daily combined with PegIFN/RBV for 24 or 48 weeks, with 3-day lead-in phase of PegIFN/RBV, in treatment-naive patients
    Interventions:
    • Drug: Arm 3 BI 201335 NA
    • Drug: Arm 3 PegIFN/RBV
  • 1. Placebo
    PegIFN/RBV for 48 weeks in treatment-naive patients
    Intervention: Drug: Arm 1 PegIFN/RBV
  • Experimental: 4 .120 mg QD / LI
    120mg BI 201335 NA once daily combined with PegIFN/RBV for 24 or 48 weeks in treatment-naive patients
    Interventions:
    • Drug: Arm 4 BI 201335 NA
    • Drug: Arm 4 PegIFN/RBV
  • Experimental: 5. 240 mg QD
    240mg BI 201335 NA once daily combined with PegIFN/RBV for 24 or 48 weeks in treatment-experienced patients
    Interventions:
    • Drug: Arm 5 BI 201335 NA
    • Drug: Arm 5 PegIFN/RBV
  • Experimental: 6. 240 mg QD / LI
    240mg BI 201335 NA once daily combined with PegIFN/RBV for 24 or 48 weeks, with 3-day lead-in phase of PegIFN/RBV, in treatment-experienced patients
    Interventions:
    • Drug: Arm 6 BI 201335 NA
    • Drug: Arm 6 PegIFN/RBV
  • Experimental: 7. 240 mg BID / LI
    240mg BI 201335 NA twice daily combined with PegIFN/RBV for 24 or 48 weeks, with 3-day lead-in phase of PegIFN/RBV, in treatment-experienced patients
    Interventions:
    • Drug: Arm 7 BI 201335 NA
    • Drug: Arm 7 PegIFN/RBV
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
719
Not Provided
November 2011   (final data collection date for primary outcome measure)

Inclusion criteria:

chronic HCV GT1; therapy-naive to IFN, PegIFN, or RBV; HCV VL >=100,000 IU/mL Liver biopsy within 2 years prior to study enrolment showing necroinflammatory activity or presence of fibrosis Normal retinal finding on fundoscopy within 6 months prior to Day 1 age 18-65 years Females and males with adequate contraception

Exclusion criteria:

Mixed genotype (1/2, 1/3, or 1/4), diagnosed by genotypic testing at screening Previous treatment with protease inhibitor Evidence of liver disease due to causes other than chronic HCV infection HIV-1 or HIV-2 positive HBV positive Decompensated liver disease, or history of decompensated liver disease Active or suspected malignancy or history of malignancy within the last 5 years History of alcohol or drug abuse within the past 12 months. Usage of any investigational drug within 30 days prior to enrolment, or 5 half-lives, whichever is longer Known hypersensitivity to any ingredient of the study drugs Condition that is defined as one which in the opinion of the investigator may put the patient at risk because of participation in the study or may influence the results of the study or the patient's ability to participate in the study Alpha-fetoprotein value > 100ng/mL at screening; if >20ng/mL and <=100ng/mL, patients can be included if there is no evidence of liver cancer in two congruent imaging studies Total bilirubin > 1.5x ULN wiht ratio of direct/indirect >1. ALT or AST levels > 5x ULN INR prolonged to >1.5x ULN Exclusion criteria related to PegIFN and/or RBV restrictions.

Both
18 Years to 65 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Argentina,   Australia,   Austria,   Canada,   Czech Republic,   France,   Germany,   Korea, Republic of,   Netherlands,   Portugal,   Romania,   Spain,   Switzerland,   United Kingdom
 
NCT00774397
1220.5, 2008-003538-11
Not Provided
Boehringer Ingelheim
Boehringer Ingelheim
Not Provided
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
Boehringer Ingelheim
July 2014

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