Hepatitis C, Chronic, Liver Cirrhosis
Conditions
Brief summary
Study to assess the antiviral efficacy, pharmacokinetics, and tolerability of 200 mg BILN 2061 ZW in a polyethylene glycol 400 (PEG 400: ethanol) drinking solution given orally for two days bid to patients with cirrhosis and chronic Hepatitis C Virus (HCV) infection
Interventions
DRUGBILN 2061 ZW
DRUGPlacebo
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Female or male sex, age of 18 years or older * Chronic Hepatitis C virus (HCV) infection * Liver biopsy consistent with active HCV infection obtained within the last 36 months. * No previous clinical evidence of decompensated cirrhosis. Present cirrhosis status consistent with grade A, according to Child-Turcotte-Pugh classification, confirmed at screening * No evidence of significant gastroesophageal varices (\> grade 1 or other risk factors) according to fiberoptic endoscopy performed within the last 12 months * No evidence of Hepatocellular carcinoma (HCC) by ultrasound performed at screening * Written informed consent consistent with International Committee on Harmonization (ICH) / Good Clinical Practice (GCP) and local legislation given prior to any study procedures * HCV of genotype I * HCV load greater than 50,000 copies messenger ribonucleic acid (mRNA) per ml serum at screening
Exclusion criteria
* Women of childbearing potential or breastfeeding women. Postmenopausal women less than 6 months after last menses, surgically sterilized or hysterectomised less than 3 months after operation or not having negative serum pregnancy test * Males not using an adequate form of contraception (condom, sterilization at least 6 months post operation) in case their partner is of childbearing potential (criteria see above) 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 gastroesophageal varices * Any histological evidence of hepatocytic dysplasia * Following serological constellations: Hepatitis B surface (HBs)-Ag positive OR anti-Hepatitis B core (HBc) positive with anti- HBs negative OR anti-HAV IgM positive OR anti-Human immunodeficiency Virus (HIV) positive * History of abuse of alcohol within the past twelve months * Planned or concurrent usage of any other pharmacological therapy at screening, including any antiviral therapy * Any concurrent infectious disease requiring antimicrobial treatment * History of malignancy (except for previously cured squamous cell or basal cell carcinoma of the skin) * Usage of any investigational drug within thirty (30) days prior to enrolment; or the planned usage of an investigational drug during the course of the current study * Known hypersensitivity to drugs * Inability to comply with the protocol * Prior or present Child´s B or C liver diseases - * Bilirubin - refer to following exclusion criterion * Prothrombin time \< 70% * Albumin \< 3.5 g/dl * Clinical evidence of ascites * Clinical evidence of encephalopathy * Clinically apparent jaundice or a total bilirubin or alkaline phosphatase exceeding 2.0 x upper limit of normal (ULN) at screening * ALT or AST \>= 10 x ULN at screening * A platelet count of less than 80.000 platelets per mm3 at screening * White blood cell count of less than 2,000 cells per mm3 at screening * AFP \> 100 ng/ml * Splenectomy * Positive test for illicit or unprescribed drugs or medications at screening. Positive test for cannabis may be allowed if the investigator assesses this result not as clinically significant * Patients with any clinically significant laboratory abnormalities based on the investigator's medical assessment at screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Virus load (VL) as determined by number of copies of HCV mRNA per ml serum | up to day 14 | Cobas Amplicor HCV Monitor v 2.0 (HCM-2.0, Roche Diagnostics) |
Secondary
| Measure | Time frame |
|---|---|
| Maximum concentration in plasma after a single dose administration (Cmax) | up to day 4 |
| Area under the plasma concentration-time curve from t = 0 to t = .τ rate (AUC0-τ) | up to day 4 |
| Time to reach Cmax following a single dose administration (tmax) | up to day 4 |
| Number of patients with relevant drug-induced changes in alanine aminotransferase (ALT) | up to day 14 |
| Number of patients with relevant drug-induced changes in aspartate aminotransferase (AST) | up to day 14 |
| Number of patients with relevant drug-induced changes in vital signs (pulse rate, systolic and diastolic blood pressure) | up to day 14 |
| Number of patients with relevant drug-induced changes in electrocardiography (ECG) | up to day 14 |
| Number of patients with relevant drug-induced changes in routine laboratory tests | up to day 14 |
| Number of patients with adverse events | up to 35 days |
| Total oral clearance of drug from plasma after oral administration, divided by F (CL/F) | up to day 4 |
| Apparent volume of distribution during the terminal elimination phase (Vz/F) | up to day 4 |
| Assessment of tolerability by investigator on a 4-point scale | day 3 |
Outcome results
None listed