<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02226939</url>
  </required_header>
  <id_info>
    <org_study_id>605.9</org_study_id>
    <nct_id>NCT02226939</nct_id>
  </id_info>
  <brief_title>Antiviral Efficacy, Pharmacokinetics and Safety of BILN 2061 ZW in Patients With Cirrhosis and Chronic Hepatitis C</brief_title>
  <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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Boehringer Ingelheim</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Boehringer Ingelheim</source>
  <brief_summary>
    <textblock>
      Study to assess the antiviral efficacy, pharmacokinetics, and tolerability of 200 mg BILN&#xD;
      2061 ZW in a polyethylene glycol 400 (PEG 400: ethanol) drinking solution given orally for&#xD;
      two days bid to patients with cirrhosis and chronic Hepatitis C Virus (HCV) infection&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>September 2002</start_date>
  <primary_completion_date type="Actual">November 2002</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Virus load (VL) as determined by number of copies of HCV mRNA per ml serum</measure>
    <time_frame>up to day 14</time_frame>
    <description>Cobas Amplicor HCV Monitor v 2.0 (HCM-2.0, Roche Diagnostics)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of patients with relevant drug-induced changes in alanine aminotransferase (ALT)</measure>
    <time_frame>up to day 14</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with relevant drug-induced changes in aspartate aminotransferase (AST)</measure>
    <time_frame>up to day 14</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with relevant drug-induced changes in vital signs (pulse rate, systolic and diastolic blood pressure)</measure>
    <time_frame>up to day 14</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with relevant drug-induced changes in electrocardiography (ECG)</measure>
    <time_frame>up to day 14</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with relevant drug-induced changes in routine laboratory tests</measure>
    <time_frame>up to day 14</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with adverse events</measure>
    <time_frame>up to 35 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum concentration in plasma after a single dose administration (Cmax)</measure>
    <time_frame>up to day 4</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the plasma concentration-time curve from t = 0 to t = .τ rate (AUC0-τ)</measure>
    <time_frame>up to day 4</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to reach Cmax following a single dose administration (tmax)</measure>
    <time_frame>up to day 4</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total oral clearance of drug from plasma after oral administration, divided by F (CL/F)</measure>
    <time_frame>up to day 4</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent volume of distribution during the terminal elimination phase (Vz/F)</measure>
    <time_frame>up to day 4</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of tolerability by investigator on a 4-point scale</measure>
    <time_frame>day 3</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">10</enrollment>
  <condition>Liver Cirrhosis</condition>
  <condition>Hepatitis C, Chronic</condition>
  <arm_group>
    <arm_group_label>BILN 2061 ZW</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BILN 2061 ZW</intervention_name>
    <arm_group_label>BILN 2061 ZW</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Female or male sex, age of 18 years or older&#xD;
&#xD;
          -  Chronic Hepatitis C virus (HCV) infection&#xD;
&#xD;
          -  Liver biopsy consistent with active HCV infection obtained within the last 36 months.&#xD;
&#xD;
          -  No previous clinical evidence of decompensated cirrhosis. Present cirrhosis status&#xD;
             consistent with grade A, according to Child-Turcotte-Pugh classification, confirmed at&#xD;
             screening&#xD;
&#xD;
          -  No evidence of significant gastroesophageal varices (&gt; grade 1 or other risk factors)&#xD;
             according to fiberoptic endoscopy performed within the last 12 months&#xD;
&#xD;
          -  No evidence of Hepatocellular carcinoma (HCC) by ultrasound performed at screening&#xD;
&#xD;
          -  Written informed consent consistent with International Committee on Harmonization&#xD;
             (ICH) / Good Clinical Practice (GCP) and local legislation given prior to any study&#xD;
             procedures&#xD;
&#xD;
          -  HCV of genotype I&#xD;
&#xD;
          -  HCV load greater than 50,000 copies messenger ribonucleic acid (mRNA) per ml serum at&#xD;
             screening&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Women of childbearing potential or breastfeeding women. Postmenopausal women less than&#xD;
             6 months after last menses, surgically sterilized or hysterectomised less than 3&#xD;
             months after operation or not having negative serum pregnancy test&#xD;
&#xD;
          -  Males not using an adequate form of contraception (condom, sterilization at least 6&#xD;
             months post operation) in case their partner is of childbearing potential (criteria&#xD;
             see above) and is not using an adequate form of contraception (hormonal&#xD;
             contraceptives, oral or injectable/ implantable, intra-uterine device (IUD))&#xD;
&#xD;
          -  Any other or additional plausible cause for chronic liver disease, including the&#xD;
             presence of other viruses known or suspected to cause hepatitis&#xD;
&#xD;
          -  Evidence of gastroesophageal varices&#xD;
&#xD;
          -  Any histological evidence of hepatocytic dysplasia&#xD;
&#xD;
          -  Following serological constellations: Hepatitis B surface (HBs)-Ag positive OR&#xD;
             anti-Hepatitis B core (HBc) positive with anti- HBs negative OR anti-HAV IgM positive&#xD;
             OR anti-Human immunodeficiency Virus (HIV) positive&#xD;
&#xD;
          -  History of abuse of alcohol within the past twelve months&#xD;
&#xD;
          -  Planned or concurrent usage of any other pharmacological therapy at screening,&#xD;
             including any antiviral therapy&#xD;
&#xD;
          -  Any concurrent infectious disease requiring antimicrobial treatment&#xD;
&#xD;
          -  History of malignancy (except for previously cured squamous cell or basal cell&#xD;
             carcinoma of the skin)&#xD;
&#xD;
          -  Usage of any investigational drug within thirty (30) days prior to enrolment; or the&#xD;
             planned usage of an investigational drug during the course of the current study&#xD;
&#xD;
          -  Known hypersensitivity to drugs&#xD;
&#xD;
          -  Inability to comply with the protocol&#xD;
&#xD;
          -  Prior or present Child´s B or C liver diseases -&#xD;
&#xD;
               -  Bilirubin - refer to following exclusion criterion&#xD;
&#xD;
               -  Prothrombin time &lt; 70%&#xD;
&#xD;
               -  Albumin &lt; 3.5 g/dl&#xD;
&#xD;
               -  Clinical evidence of ascites&#xD;
&#xD;
               -  Clinical evidence of encephalopathy&#xD;
&#xD;
          -  Clinically apparent jaundice or a total bilirubin or alkaline phosphatase exceeding&#xD;
             2.0 x upper limit of normal (ULN) at screening&#xD;
&#xD;
          -  ALT or AST &gt;= 10 x ULN at screening&#xD;
&#xD;
          -  A platelet count of less than 80.000 platelets per mm3 at screening&#xD;
&#xD;
          -  White blood cell count of less than 2,000 cells per mm3 at screening&#xD;
&#xD;
          -  AFP &gt; 100 ng/ml&#xD;
&#xD;
          -  Splenectomy&#xD;
&#xD;
          -  Positive test for illicit or unprescribed drugs or medications at screening. Positive&#xD;
             test for cannabis may be allowed if the investigator assesses this result not as&#xD;
             clinically significant&#xD;
&#xD;
          -  Patients with any clinically significant laboratory abnormalities based on the&#xD;
             investigator's medical assessment at screening&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <link>
    <url>http://trials.boehringer-ingelheim.com</url>
    <description>Related Info</description>
  </link>
  <verification_date>August 2014</verification_date>
  <study_first_submitted>August 26, 2014</study_first_submitted>
  <study_first_submitted_qc>August 26, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 27, 2014</study_first_posted>
  <last_update_submitted>August 26, 2014</last_update_submitted>
  <last_update_submitted_qc>August 26, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 27, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hepatitis A</mesh_term>
    <mesh_term>Hepatitis C</mesh_term>
    <mesh_term>Hepatitis C, Chronic</mesh_term>
    <mesh_term>Hepatitis</mesh_term>
    <mesh_term>Liver Cirrhosis</mesh_term>
    <mesh_term>Fibrosis</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02226939
org study id: 605.9
nct id: NCT02226939
lead sponsor: 
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
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double
measure: Virus load (VL) as determined by number of copies of HCV mRNA per ml serum
time frame: up to day 14
description: Cobas Amplicor HCV Monitor v 2.0 (HCM-2.0, Roche Diagnostics)
measure: Number of patients with relevant drug-induced changes in alanine aminotransferase (ALT)
time frame: up to day 14
measure: Number of patients with relevant drug-induced changes in aspartate aminotransferase (AST)
time frame: up to day 14
measure: Number of patients with relevant drug-induced changes in vital signs (pulse rate, systolic and diastolic blood pressure)
time frame: up to day 14
measure: Number of patients with relevant drug-induced changes in electrocardiography (ECG)
time frame: up to day 14
measure: Number of patients with relevant drug-induced changes in routine laboratory tests
time frame: up to day 14
measure: Number of patients with adverse events
time frame: up to 35 days
measure: Maximum concentration in plasma after a single dose administration (Cmax)
time frame: up to day 4
measure: Area under the plasma concentration-time curve from t = 0 to t = .τ rate (AUC0-τ)
time frame: up to day 4
measure: Time to reach Cmax following a single dose administration (tmax)
time frame: up to day 4
measure: Total oral clearance of drug from plasma after oral administration, divided by F (CL/F)
time frame: up to day 4
measure: Apparent volume of distribution during the terminal elimination phase (Vz/F)
time frame: up to day 4
measure: Assessment of tolerability by investigator on a 4-point scale
time frame: day 3
arm group label: BILN 2061 ZW
arm group type: Experimental
arm group label: Placebo
arm group type: Placebo Comparator
intervention type: Drug
intervention name: BILN 2061 ZW
arm group label: BILN 2061 ZW
intervention type: Drug
intervention name: Placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
url: http://trials.boehringer-ingelheim.com
description: Related Info
responsible party type: Sponsor
mesh term: Hepatitis A
mesh term: Hepatitis C
mesh term: Hepatitis C, Chronic
mesh term: Hepatitis
mesh term: Liver Cirrhosis
mesh term: Fibrosis