Safety, Antiviral Activity and PK of MRD of BI 201335 in Chronic Hepatitis C Patients Both Treatment Naive and -Experienced

NCT ID: NCT00793793

Last Updated: 2018-09-05

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

96 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-09-30

Study Completion Date

2011-01-25

Brief Summary

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This study will investigate safety, antiviral activity, and pharmacokinetics of BI 201335 NA in HCV genotype 1 infected patients treated for 14 days monotherapy followed by BI 201335 NA combination therapy with PegIFN/RBV for an additional 14 days for treatment-naïve patients; or for 28 days as BI 201335 NA combination therapy with PegIFN/RBV for treatment-experienced patients.

A secondary objective is to investigate antiviral activity, potential drug-drug interactions and safety of combination therapy of BI 201335 NA and PegIFN/RBV up to 28 days for treatment-naïve patients.

Detailed Description

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Conditions

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Hepatitis C, Chronic

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Study Groups

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20mg

patient to receive 20mg solution BI201335 qd +/- PegIFN/RBV fore 28 days

Group Type EXPERIMENTAL

BI201335

Intervention Type DRUG

patient to receive 240mg solution BI201335 qd +/- PegIFN/RBV fore 28 days

48mg

patient to receive 48mg solution BI201335 qd +/- PegIFN/RBV fore 28 days

Group Type EXPERIMENTAL

BI201335

Intervention Type DRUG

patient to receive rising doses of BI201335 solution qd +/- PegIFN/RBV fore 28 days

120mg

patient to receive 120mg solution BI201335 qd +/- PegIFN/RBV fore 28 days

Group Type EXPERIMENTAL

BI201335

Intervention Type DRUG

patient to receive rising doses of BI201335 solution qd +/- PegIFN/RBV fore 28 days

240mg

patient to receive 240mg solution BI201335 qd +/- PegIFN/RBV fore 28 days

Group Type EXPERIMENTAL

BI201335

Intervention Type DRUG

patient to receive rising doses of BI201335 solution qd +/- PegIFN/RBV fore 28 days

Placebo

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Interventions

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BI201335

patient to receive rising doses of BI201335 solution qd +/- PegIFN/RBV fore 28 days

Intervention Type DRUG

BI201335

patient to receive rising doses of BI201335 solution qd +/- PegIFN/RBV fore 28 days

Intervention Type DRUG

BI201335

patient to receive rising doses of BI201335 solution qd +/- PegIFN/RBV fore 28 days

Intervention Type DRUG

BI201335

patient to receive 240mg solution BI201335 qd +/- PegIFN/RBV fore 28 days

Intervention Type DRUG

Placebo

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1a. For treatment-naïve patients: no prior therapy with interferon, peginterferon, or ribavirin for acute or chronic hepatitis C infection

1b. For treatment-experienced patients: confirmed virological failure during or after combination treatment with an approved dose of alfa-2a or alfa-2b peginterferon combined with ribavirin; such patients must have received at least 12 weeks of therapy with a 90 day washout period prior to screening and must have documentation of medical history prior to enrolment in 1220.2 2. Age 18 years or older 3. Signed informed consent form prior to trial participation 4. Male or female with documented hysterectomy or menopausal female with last menstrual period at least 6 months prior to screening 5. Chronic hepatitis C infection of genotype 1, diagnosed by positive HCV serology test (HCV Ab positive) or detectable HCV RNA at least 6 months prior to screening 6. HCV viral load \>= 100,000 IU/mL at screening 7. TSH and T4 within normal limits or adequately controlled thyroid function 8. Histological evidence within 36 months prior to study enrolment of any degree of chronic necroinflammatory activity or the presence of fibrosis (Ishak Grade 1-4 or Metavir Grade 1-3)

Exclusion Criteria

1. Patients who have been previously treated with at least one dose of any protease inhibitor for acute or chronic hepatitis C infection
2. Evidence of liver disease due to causes other than chronic HCV infection
3. Positive ELISA for HIV-1 or HIV-2
4. Hepatitis B virus (HBV) infection based on presence of Hbs Ag or HBV DNA
5. Any previous liver biopsy consistent with cirrhosis
6. Decompensated liver diseases as evidenced by ascites, portal hypertension, jaundice or hepatic encephalopathy
7. Haemophilia
8. Hemoglobinopathy (e.g., thalassemia major or sickle cell anemia)
9. Severe pre-existing psychiatric disease
10. Poorly controlled diabetes mellitus
11. Ischaemic heart disease
12. Chronic obstructive airway disease
13. Autoimmune disease; including autoimmune hepatitis
14. History of alcohol abuse within the past 12 months
15. Hyperbilirubinemia (conjugated bilirubin) \>1.5x ULN
16. Alkaline phosphatase \>1.5x ULN
17. ALT and AST levels \>= 5 x ULN
18. Hemoglobin \< 12.0 g/dL for women and \< 13.0 g/dL for men
19. White blood cell count \< 2000 cells/mm3
20. Absolute Neutrophil Count \< 1500 cells/mm3
21. Platelet count \< 100,000 cells/mm3
22. Prothrombin time INR (Institutional Normalized Ratio) prolonged to \> 1.5 x ULN
23. Usage of any investigational drug within 30 days prior to enrolment; or the planned usage of an investigational drug during the course of the current study
24. Known hypersensitivity to study drugs
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Boehringer Ingelheim

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Boehringer Ingelheim

Role: STUDY_CHAIR

Boehringer Ingelheim

Locations

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1220.2.10 Boehringer Ingelheim Investigational Site

San Francisco, California, United States

Site Status

1220.2.15 Boehringer Ingelheim Investigational Site

San Francisco, California, United States

Site Status

1220.2.17 Boehringer Ingelheim Investigational Site

Baltimore, Maryland, United States

Site Status

1220.2.11 Boehringer Ingelheim Investigational Site

New York, New York, United States

Site Status

1220.2.12 Boehringer Ingelheim Investigational Site

New York, New York, United States

Site Status

1220.2.14 Boehringer Ingelheim Investigational Site

Austin, Texas, United States

Site Status

1220.2.3304A Boehringer Ingelheim Investigational Site

Lyon, , France

Site Status

1220.2.3303A Boehringer Ingelheim Investigational Site

Marseille, , France

Site Status

1220.2.3301A Boehringer Ingelheim Investigational Site

Paris, , France

Site Status

1220.2.3302A Boehringer Ingelheim Investigational Site

Paris, , France

Site Status

1220.2.49002 Boehringer Ingelheim Investigational Site

Berlin, , Germany

Site Status

1220.2.49005 Boehringer Ingelheim Investigational Site

Düsseldorf, , Germany

Site Status

1220.2.49006 Boehringer Ingelheim Investigational Site

Hanover, , Germany

Site Status

1220.2.49004 Boehringer Ingelheim Investigational Site

Kiel, , Germany

Site Status

1220.2.49003 Boehringer Ingelheim Investigational Site

Mainz, , Germany

Site Status

1220.2.34001 Boehringer Ingelheim Investigational Site

Madrid, , Spain

Site Status

Countries

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United States France Germany Spain

References

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Berger KL, Lagace L, Triki I, Cartier M, Marquis M, Lawetz C, Bethell R, Scherer J, Kukolj G. Viral resistance in hepatitis C virus genotype 1-infected patients receiving the NS3 protease inhibitor Faldaprevir (BI 201335) in a phase 1b multiple-rising-dose study. Antimicrob Agents Chemother. 2013 Oct;57(10):4928-36. doi: 10.1128/AAC.00822-13. Epub 2013 Jul 22.

Reference Type DERIVED
PMID: 23877706 (View on PubMed)

Manns MP, Bourliere M, Benhamou Y, Pol S, Bonacini M, Trepo C, Wright D, Berg T, Calleja JL, White PW, Stern JO, Steinmann G, Yong CL, Kukolj G, Scherer J, Boecher WO. Potency, safety, and pharmacokinetics of the NS3/4A protease inhibitor BI201335 in patients with chronic HCV genotype-1 infection. J Hepatol. 2011 Jun;54(6):1114-22. doi: 10.1016/j.jhep.2010.08.040. Epub 2010 Nov 11.

Reference Type DERIVED
PMID: 21145839 (View on PubMed)

Other Identifiers

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2007-001158-19

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

1220.2

Identifier Type: -

Identifier Source: org_study_id

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