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

Phase 2

Completed

• Conditions: Liver Cirrhosis; Hepatitis C, Chronic
• Interventions: Drug: Placebo; Drug: BILN 2061 ZW

• Registration Number: NCT02226939
• Lead Sponsor: Boehringer Ingelheim

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

Detailed Description

Not available

Study Timeline

• Study Start: 2002-09
• Primary Completion: 2002-11
• Status Verified: 2014-08
• Study First Submitted: 2014-08-26
• Study First Submitted QC: 2014-08-26
• Last Update Submitted: 2014-08-26
• Study First Posted: 2014-08-27
• Last Update Posted: 2014-08-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 10

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	-
BILN 2061 ZW	BILN 2061 ZW	-

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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
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
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