Antiviral Efficacy, Pharmacokinetics and Safety of BILN 2061 ZW in Patients With Cirrhosis and Chronic Hepatitis C
Antiviral Efficacy, Pharmacokinetics and Safety of BILN 2061 ZW in Patients With Cirrhosis and Chronic Hepatitis C
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
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