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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Locations
United States, California
1220.5.0008 Boehringer Ingelheim Investigational Site
San Francisco, California, United States
1220.5.0001 Boehringer Ingelheim Investigational Site
San Francisco, California, United States
United States, Illinois
1220.5.0005 Boehringer Ingelheim Investigational Site
Chicago, Illinois, United States
United States, Maryland
1220.5.0006 Boehringer Ingelheim Investigational Site
Lutherville, Maryland, United States
United States, New York
1220.5.0003 Boehringer Ingelheim Investigational Site
New York, New York, United States
1220.5.0002 Boehringer Ingelheim Investigational Site
New York, New York, United States
United States, Pennsylvania
1220.5.0007 Boehringer Ingelheim Investigational Site
Philadelphia, Pennsylvania, United States
United States, Tennessee
1220.5.0010 Boehringer Ingelheim Investigational Site
Germantown, Tennessee, United States
1220.5.0009 Boehringer Ingelheim Investigational Site
Nashville, Tennessee, United States
United States, Texas
1220.5.0004 Boehringer Ingelheim Investigational Site
Austin, Texas, United States
Argentina
1220.5.5401 Boehringer Ingelheim Investigational Site
Capital Federal, Argentina
1220.5.5403 Boehringer Ingelheim Investigational Site
Capital Federal, Argentina
1220.5.5405 Boehringer Ingelheim Investigational Site
Derqui, Pilar, Argentina
1220.5.5402 Boehringer Ingelheim Investigational Site
Rosario, Argentina
1220.5.5406 Boehringer Ingelheim Investigational Site
Rosario, Argentina
Australia, New South Wales
1220.5.6110 Boehringer Ingelheim Investigational Site
Camperdown, New South Wales, Australia
1220.5.6109 Boehringer Ingelheim Investigational Site
Kogarah, New South Wales, Australia
1220.5.6105 Boehringer Ingelheim Investigational Site
Randwick, New South Wales, Australia
1220.5.6101 Boehringer Ingelheim Investigational Site
Westmead, New South Wales, Australia
Australia, Queensland
1220.5.6103 Boehringer Ingelheim Investigational Site
Herston, Queensland, Australia
1220.5.6104 Boehringer Ingelheim Investigational Site
Woolloongabba, Queensland, Australia
Australia, Victoria
1220.5.6102 Boehringer Ingelheim Investigational Site
Clayton, Victoria, Australia
1220.5.6107 Boehringer Ingelheim Investigational Site
Fitzroy, Victoria, Australia
1220.5.6108 Boehringer Ingelheim Investigational Site
Parkville, Victoria, Australia
Austria
1220.5.4303 Boehringer Ingelheim Investigational Site
Linz, Austria
1220.5.4301 Boehringer Ingelheim Investigational Site
Wien, Austria
1220.5.4302 Boehringer Ingelheim Investigational Site
Wien, Austria
Canada, Alberta
1220.5.1003 Boehringer Ingelheim Investigational Site
Edmonton, Alberta, Canada
Canada, British Columbia
1220.5.1007 Boehringer Ingelheim Investigational Site
Vancouver, British Columbia, Canada
Canada, Ontario
1220.5.1006 Boehringer Ingelheim Investigational Site
Hamilton, Ontario, Canada
1220.5.1001 Boehringer Ingelheim Investigational Site
Ottawa, Ontario, Canada
1220.5.1002 Boehringer Ingelheim Investigational Site
Toronto, Ontario, Canada
Canada, Quebec
1220.5.1004 Boehringer Ingelheim Investigational Site
Montreal, Quebec, Canada
Czech Republic
1220.5.4202 Boehringer Ingelheim Investigational Site
Melnik, Czech Republic
1220.5.4203 Boehringer Ingelheim Investigational Site
Opava, Czech Republic
France
1220.5.3301A Boehringer Ingelheim Investigational Site
Clichy, France
1220.5.3307A Boehringer Ingelheim Investigational Site
Creteil, France
1220.5.3309A Boehringer Ingelheim Investigational Site
Lyon, France
1220.5.3304A Boehringer Ingelheim Investigational Site
Marseille, France
1220.5.3306A Boehringer Ingelheim Investigational Site
Montpellier, France
1220.5.3303A Boehringer Ingelheim Investigational Site
Paris, France
1220.5.3302A Boehringer Ingelheim Investigational Site
Paris, France
1220.5.3308A Boehringer Ingelheim Investigational Site
Paris Cedex 20, France
1220.5.3305A Boehringer Ingelheim Investigational Site
Vandoeuvre Cedex, France
Germany
1220.5.4902 Boehringer Ingelheim Investigational Site
Berlin, Germany
1220.5.4917 Boehringer Ingelheim Investigational Site
Berlin, Germany
1220.5.4903 Boehringer Ingelheim Investigational Site
Berlin, Germany
1220.5.4914 Boehringer Ingelheim Investigational Site
Bochum, Germany
1220.5.4913 Boehringer Ingelheim Investigational Site
Bonn, Germany
1220.5.4915 Boehringer Ingelheim Investigational Site
Dortmund, Germany
1220.5.4905 Boehringer Ingelheim Investigational Site
Düsseldorf, Germany
1220.5.4912 Boehringer Ingelheim Investigational Site
Düsseldorf, Germany
1220.5.4906 Boehringer Ingelheim Investigational Site
Frankfurt/Main, Germany
1220.5.4908 Boehringer Ingelheim Investigational Site
Hamburg, Germany
1220.5.4904 Boehringer Ingelheim Investigational Site
Hannover, Germany
1220.5.4910 Boehringer Ingelheim Investigational Site
Leipzig, Germany
1220.5.4909 Boehringer Ingelheim Investigational Site
Mainz, Germany
1220.5.4907 Boehringer Ingelheim Investigational Site
Tübingen, Germany
Korea, Republic of
1220.5.8210 Boehringer Ingelheim Investigational Site
Busan, Korea, Republic of
1220.5.8205 Boehringer Ingelheim Investigational Site
Daegu, Korea, Republic of
1220.5.8201 Boehringer Ingelheim Investigational Site
Pusan, Korea, Republic of
1220.5.8202 Boehringer Ingelheim Investigational Site
Seoul, Korea, Republic of
1220.5.8206 Boehringer Ingelheim Investigational Site
Seoul, Korea, Republic of
1220.5.8207 Boehringer Ingelheim Investigational Site
Seoul, Korea, Republic of
1220.5.8208 Boehringer Ingelheim Investigational Site
Seoul, Korea, Republic of
1220.5.8204 Boehringer Ingelheim Investigational Site
Seoungnam, Korea, Republic of
1220.5.8203 Boehringer Ingelheim Investigational Site
Sungnam, Korea, Republic of
1220.5.8209 Boehringer Ingelheim Investigational Site
Suwon, Korea, Republic of
1220.5.8211 Boehringer Ingelheim Investigational Site
Yangsan, Korea, Republic of
Netherlands
1220.5.3101 Boehringer Ingelheim Investigational Site
Amsterdam, Netherlands
1220.5.3102 Boehringer Ingelheim Investigational Site
Leiden, Netherlands
Portugal
1220.5.3501 Boehringer Ingelheim Investigational Site
Coimbra, Portugal
1220.5.3504 Boehringer Ingelheim Investigational Site
Coimbra, Portugal
1220.5.3502 Boehringer Ingelheim Investigational Site
Lisboa, Portugal
1220.5.3503 Boehringer Ingelheim Investigational Site
Lisboa, Portugal
1220.5.3506 Boehringer Ingelheim Investigational Site
Porto, Portugal
1220.5.3507 Boehringer Ingelheim Investigational Site
Porto, Portugal
Romania
1220.5.4003 Boehringer Ingelheim Investigational Site
Bucharest, Romania
1220.5.4004 Boehringer Ingelheim Investigational Site
Bucharest, Romania
1220.5.4002 Boehringer Ingelheim Investigational Site
Bucharest, Romania
1220.5.4001 Boehringer Ingelheim Investigational Site
Bucharest, Romania
Spain
1220.5.3405 Boehringer Ingelheim Investigational Site
Barcelona, Spain
1220.5.3402 Boehringer Ingelheim Investigational Site
Barcelona, Spain
1220.5.3406 Boehringer Ingelheim Investigational Site
Madrid, Spain
1220.5.3404 Boehringer Ingelheim Investigational Site
Madrid, Spain
1220.5.3403 Boehringer Ingelheim Investigational Site
Madrid, Spain
1220.5.3401 Boehringer Ingelheim Investigational Site
Madrid, Spain
Switzerland
1220.5.4104 Boehringer Ingelheim Investigational Site
Bern, Switzerland
1220.5.4102 Boehringer Ingelheim Investigational Site
La Chaux-de-Fonds, Switzerland
1220.5.4103 Boehringer Ingelheim Investigational Site
Lugano, Switzerland
1220.5.4101 Boehringer Ingelheim Investigational Site
Zürich, Switzerland
1220.5.4106 Boehringer Ingelheim Investigational Site
Zürich, Switzerland
United Kingdom
1220.5.4405 Boehringer Ingelheim Investigational Site
Bristol, United Kingdom
1220.5.4402 Boehringer Ingelheim Investigational Site
London, United Kingdom
1220.5.4401 Boehringer Ingelheim Investigational Site
London, United Kingdom
1220.5.4406 Boehringer Ingelheim Investigational Site
London, United Kingdom
1220.5.4410 Boehringer Ingelheim Investigational Site
London, United Kingdom
1220.5.4409 Boehringer Ingelheim Investigational Site
London, United Kingdom
1220.5.4408 Boehringer Ingelheim Investigational Site
Nottingham, United Kingdom
1220.5.4403 Boehringer Ingelheim Investigational Site
Southampton, United Kingdom
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
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Hepatitis, Chronic

ClinicalTrials.gov processed this record on October 01, 2014