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

Liver Cirrhosis Clinical Trial

Official title:

A Randomised, Double-blind, Placebo Controlled Trial With 200 mg BILN 2061 ZW Given p.o. at Two Consecutive Days Bid to Investigate the Antiviral Efficacy, Pharmacokinetics, Safety in Patients With Cirrhosis and Chronic Hepatitis C

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02226939
• Other study ID #: 605.9
• Status: Completed
• Phase: Phase 2
• First received: August 26, 2014
• Last updated: August 26, 2014
• Start date: September 2002

Study information

• Verified date: August 2014
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. primary completion date: November 2002
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

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

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C, Chronic
• Hepatitis, Chronic
• Liver Cirrhosis

Intervention

Drug:
• BILN 2061 ZW

• Placebo

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Virus load (VL) as determined by number of copies of HCV mRNA per ml serum	Cobas Amplicor HCV Monitor v 2.0 (HCM-2.0, Roche Diagnostics)	up to day 14	No
Secondary	Number of patients with relevant drug-induced changes in alanine aminotransferase (ALT)		up to day 14	No
Secondary	Number of patients with relevant drug-induced changes in aspartate aminotransferase (AST)		up to day 14	No
Secondary	Number of patients with relevant drug-induced changes in vital signs (pulse rate, systolic and diastolic blood pressure)		up to day 14	No
Secondary	Number of patients with relevant drug-induced changes in electrocardiography (ECG)		up to day 14	No
Secondary	Number of patients with relevant drug-induced changes in routine laboratory tests		up to day 14	No
Secondary	Number of patients with adverse events		up to 35 days	No
Secondary	Maximum concentration in plasma after a single dose administration (Cmax)		up to day 4	No
Secondary	Area under the plasma concentration-time curve from t = 0 to t = .t rate (AUC0-t)		up to day 4	No
Secondary	Time to reach Cmax following a single dose administration (tmax)		up to day 4	No
Secondary	Total oral clearance of drug from plasma after oral administration, divided by F (CL/F)		up to day 4	No
Secondary	Apparent volume of distribution during the terminal elimination phase (Vz/F)		up to day 4	No
Secondary	Assessment of tolerability by investigator on a 4-point scale		day 3	No

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