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
  Purpose

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.


Condition Intervention Phase
Hepatitis C, Chronic
Drug: Arm 3 BI 201335 NA
Drug: Arm 3 PegIFN/RBV
Drug: Arm 4 BI 201335 NA
Drug: Arm 4 PegIFN/RBV
Drug: Arm 5 BI 201335 NA
Drug: Arm 5 PegIFN/RBV
Drug: Arm 6 BI 201335 NA
Drug: Arm 6 PegIFN/RBV
Drug: Arm 7 BI 201335 NA
Drug: Arm 7 PegIFN/RBV
Drug: Arm 1 PegIFN/RBV
Drug: Arm 2 BI 201335 NA
Drug: Arm 2 PegIFN/RBV
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: 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)

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 719
Study Start Date: October 2008
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 2. 240 mg QD
240mg BI 201335 NA once daily combined with PegIFN/RBV for 24 or 48weeks, in treatment-naive patients
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: 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
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
1. Placebo
PegIFN/RBV for 48 weeks in treatment-naive patients
Drug: Arm 1 PegIFN/RBV
PegIFN (180 µg/wk) and RBV (1000/1200mg/d),48 weeks
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
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
Experimental: 5. 240 mg QD
240mg BI 201335 NA once daily combined with PegIFN/RBV for 24 or 48 weeks in treatment-experienced patients
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
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
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
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
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

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.

  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00774397

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Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

No publications provided

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT00774397     History of Changes
Other Study ID Numbers: 1220.5, 2008-003538-11
Study First Received: October 16, 2008
Last Updated: July 10, 2014
Health Authority: Argentina: A.N.M.A.T. (Administracion Nacional de Medicamentos, Alimentos y Tecnología Médica).
Australia: Dept of Health and Ageing Therapeutic Goods Admin
Austria: Federal Office for Safety in Health Care
Canada: Health Canada - Therapeutic Products Directorate
Czech Republic: State Institute for Drug Control (SUKL), CZ-100 41 Prague 10
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: BfArM (Bundesagentur für Arzneimittel und Medizinalproduke)
Korea, Republic of: Korea Food and Drug Administration
Netherlands: Central Committee on Research Involving Human Subjects (CCMO)
Portugal: National Pharmacy and Medicines Institute
Romania: National Medicines Agency, Bucharest
Spain: Spanish Agency for Medicines and Health Products
Switzerland: Swissmedic
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Hepatitis C, Chronic
Digestive System Diseases
Enterovirus Infections
Flaviviridae Infections
Hepatitis, Chronic
Hepatitis, Viral, Human
Liver Diseases
Picornaviridae Infections
RNA Virus Infections
Virus Diseases

ClinicalTrials.gov processed this record on October 22, 2014