Clinical trial NCT02226939: Antiviral Efficacy, Pharmacokinetics and Safety of BILN 2061 ZW in Patients With Cirrhosis and Chronic Hepatitis C
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Liver Cirrhosis
Hepatitis C, Chronic
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2014-08-27
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: Virus load (VL) as determined by number of copies of HCV mRNA per ml serum
timeFrame: up to day 14
Secondary outcomes:
measure: Number of patients with relevant drug-induced changes in alanine aminotransferase (ALT)
timeFrame: up to day 14
measure: Number of patients with relevant drug-induced changes in aspartate aminotransferase (AST)
timeFrame: up to day 14
measure: Number of patients with relevant drug-induced changes in vital signs (pulse rate, systolic and diastolic blood pressure)
timeFrame: up to day 14
measure: Number of patients with relevant drug-induced changes in electrocardiography (ECG)
timeFrame: up to day 14
measure: Number of patients with relevant drug-induced changes in routine laboratory tests
timeFrame: up to day 14
measure: Number of patients with adverse events
timeFrame: up to 35 days
measure: Maximum concentration in plasma after a single dose administration (Cmax)
timeFrame: up to day 4
measure: Area under the plasma concentration-time curve from t = 0 to t = .τ rate (AUC0-τ)
timeFrame: up to day 4
measure: Time to reach Cmax following a single dose administration (tmax)
timeFrame: up to day 4
measure: Total oral clearance of drug from plasma after oral administration, divided by F (CL/F)
timeFrame: up to day 4
measure: Apparent volume of distribution during the terminal elimination phase (Vz/F)
timeFrame: up to day 4
measure: Assessment of tolerability by investigator on a 4-point scale
timeFrame: day 3
Other outcomes:
Locations:
Study officials:
References: