Evaluation of the Antiviral Pharmacodynamic Effect, Safety, and Pharmacokinetics of Escalating Doses of BILB 1941 ZW to Patients With Chronic Hepatitis C Genotype 1 Virus Infection

Study Overview
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Brief Summary
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To assess the antiviral effect, safety and pharmacokinetics of rising doses of 10 mg, 20 mg, 40 mg, 60 mg, 80 mg, 100 mg, 150 mg, 200 mg, 300 mg, 450 mg, 650 mg, 900 mg oral BILB 1941 ZW administered Q8H in a polyethyleneglycol 400 (PEG 400): distilled water: Tromethamine (TRIS) drinking solution for five days to patients with chronic HCV genotype 1 infection

Official Title
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A Multinational Randomised, Double-blind, Placebo Controlled Study to Evaluate the Antiviral Pharmacodynamic Effect, Safety, and Pharmacokinetics of Escalating Doses of BILB 1941 ZW Oral Solution Administered Q8H for Five Days to Patients With Chronic Hepatitis C Genotype 1 Virus Infection

Conditions
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Hepatitis C, Chronic

Intervention / Treatment
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* Drug: BILB 1941 ZW
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult males from 18 - 65 years Written informed consent consistent with ICH (International Conference on Harmonisation)/GCP (Good Clinical Practice) and local legislation given prior to any study procedures Chronic HCV infection demonstrated by positive HCV IgG Antibody HCV genotype 1 which has to be confirmed by central laboratory test before Visit 2 Liver biopsy consistent with active Hepatitis C virus (HCV) infection obtained within the last 24 months showing minimal to mild liver fibrosis and without cirrhosis (Ishak or Metavir grade <= 2) HCV ribonucleic acid (RNA) load greater than 100,000 IU RNA per ml serum at screening Willing to abstain from alcohol during the screening, treatment and until completion of the study (visit 11) Exclusion Criteria: Males not using an adequate form of contraception (condom, sterilisation at least 6 months post operation) in case their partner is of childbearing potential and is not using an adequate form of contraception (hormonal contraceptives, oral or injectable/implantable, intra-uterine device (IUD). Any other or additional plausible cause for chronic liver disease, including the presence of other viruses known or suspected to cause hepatitis Evidence of decompensated liver disease: ascites, portal hypertension or hepatic encephalopathy Positive test for human immunodeficiency virus (HIV) or Hepatitis B surface (HBs) antigen at screening Current alcohol or drug abuse, or history of the same, within the past twelve (12) months. All patients must abstain from alcohol from enrolment until completion of the study (visit 11). Any concurrent medical illness or disease requiring treatment or concomitant medications History of malignancy (except for previously cured squamous cell or basal cell carcinoma) Usage of any investigational drug within thirty (30) days prior to enrolment or 5 halflives, whichever is longer; or the planned usage of an investigational drug during the course of the current study Patients treated with interferon and/or ribavirin within 6 months prior to screening Planned or concurrent usage of any other pharmacological therapy at screening, or during the trial period, including any antiviral therapy or vaccination Known hypersensitivity to drugs or excipients Patients with any one of the following laboratory values at screening: Alanine transaminase (ALT) or Aspartate transaminase (AST) > 2.5 x upper limit of normal (ULN) (at screening and during the last 3 months before screening demonstrated by at least 2 further determinations) Total bilirubin > 1x ULN Alkaline phosphatase > 1.5x ULN Prothrombin time (INR, prolonged) > 1.5 Platelet count < 100,000 / mm3 Hemoglobin < 10.5 g/dL White blood cell count < 2,000 / mm3 Patients with any clinically significant laboratory abnormalities based on the investigator's medical assessment at screening Positive urine test for drug abuse at screening Patients with known Gilbert's disease Prior randomisation to active treatment with BILB 1941 ZW into dose groups 3 - 9 of this trial, or previous re-treatment based on amendment 2. To support selection, centers will receive lists of the placebo patients of the previous dose levels, however, only for each center separately Inability to comply with the protocol

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BILB 1941 ZW<br>Escalating Doses | Drug: BILB 1941 ZW<br> <br> |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in virus load (VL) | determined by IU per ml serum from baseline by > 1.0 log10 step | Up to day 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax (maximum measured concentration of the analyte in plasma) |  | Up to 14 days after first drug administration | 
| tmax (time from dosing to maximum measured concentration of the analyte in plasma) |  | Up to 14 days after first drug administration | 
| AUCτ,1 (area under the concentration-time curve of the analyte in plasma over a uniform dosing interval τ after administration of the first dose) |  | Up to 14 days after first drug administration | 
| AUC0-∞ (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity) |  | Up to 14 days after first drug administration | 
| %AUCtz-∞ (the percentage of the AUC0-∞ that is obtained by extrapolation) |  | Up to 14 days after first drug administration | 
| λz (terminal rate constant in plasma) |  | Up to 14 days after first drug administration | 
| t1/2 (terminal half-life of the analyte in plasma) |  | Up to 14 days after first drug administration | 
| CL/F (apparent clearance of the analyte in plasma after extravascular administration) |  | Up to 14 days after first drug administration | 
| Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular administration) |  | Up to 14 days after first drug administration | 
| Number of patients with clinically significant changes in vital signs |  | Up to 14 days after first drug administration | 
| Number of patients with clinically significant changes in body temperature |  | Up to 14 days after first drug administration | 
| Number of patients with abnormal findings in electrocardiogram (ECG) |  | Up to 14 days after first drug administration | 
| Number of patients with abnormal changes in clinical laboratory parameters |  | Up to 14 days after first drug administration | 
| Number of patients with adverse events |  | Up to 14 days after first drug administration | 
| Number of patients with abnormal findings in physical examination |  | Up to 14 days after first drug administration | 
| Investigator assessed tolerability on a 4 point scale |  | Up to 14 days after first drug administration |