Safety, Antiviral Activity and PK of MRD of BI 201335 in Chronic Hepatitis C Patients Both Treatment Naive and -Experienced
Condition: Hepatitis C, Chronic
MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis; Hepatitis, Chronic
Intervention: BI201335; BI201335; BI201335; BI201335; Placebo
Intervention description: patient to receive rising doses of BI201335 solution qd +/- PegIFN/RBV fore 28 days; patient to receive rising doses of BI201335 solution qd +/- PegIFN/RBV fore 28 days; patient to receive rising doses of BI201335 solution qd +/- PegIFN/RBV fore 28 days; patient to receive 240mg solution BI201335 qd +/- PegIFN/RBV fore 28 days
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Enrollment: 96.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        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