<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/NCT02226952</url>
  </required_header>
  <id_info>
    <org_study_id>605.5</org_study_id>
    <nct_id>NCT02226952</nct_id>
  </id_info>
  <brief_title>Antiviral Efficacy, Pharmacokinetics and Safety of BILN 2061 ZW in Patients With Chronic Hepatitis C Virus Infection</brief_title>
  <official_title>A Randomised, Double-blind, Placebo Controlled Trial With 25 mg, 200 mg and 500 mg BILN 2061 ZW Given p.o. at Two Consecutive Days Bid to Investigate the Antiviral Efficacy, Pharmacokinetics, Safety in Patients With Chronic Hepatitis C Virus Infection</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 BILN 2061 ZW in&#xD;
      a polyethyleneglycol 400 (PEG 400: ethanol) drinking solution given for two days bid in&#xD;
      patients with chronic Hepatitis C Virus (HCV) infection.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>November 2001</start_date>
  <primary_completion_date type="Actual">April 2002</primary_completion_date>
  <phase>Phase 1/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) 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 clinically relevant changes in alanine aminotransferase (ALT)</measure>
    <time_frame>up to day 14</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with clinically relevant changes in aspartate aminotransferase (AST)</measure>
    <time_frame>up to day 14</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with clinically relevant changes in vital signs</measure>
    <time_frame>up to day 14</time_frame>
    <description>pulse rate, systolic and diastolic blood pressure</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with clinically relevant changes in electrocardiography (ECG)</measure>
    <time_frame>up to day 14</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with clinically relevant 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>6</number_of_arms>
  <enrollment type="Actual">51</enrollment>
  <condition>Hepatitis C, Chronic</condition>
  <arm_group>
    <arm_group_label>Group 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>BILN 2061 W, medium dose, in patients with genotype 1, minimal fibrosis</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>BILN 2061 W, high dose, in patients with genotype 1, minimal fibrosis</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>BILN 2061 W, high dose, in non-genotype 1 patients, minimal fibrosis</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 4</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>BILN 2061 W, low dose, in patients with genotype 1, minimal fibrosis</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 5</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>BILN 2061 W, medium dose, in patients with genotype 1, advanced fibrosis</description>
  </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 W, low dose</intervention_name>
    <arm_group_label>Group 4</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BILN 2061 W, medium dose</intervention_name>
    <arm_group_label>Group 1</arm_group_label>
    <arm_group_label>Group 5</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BILN 2061 W, high dose</intervention_name>
    <arm_group_label>Group 2</arm_group_label>
    <arm_group_label>Group 3</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;
          -  Active, chronic Hepatitis C virus (HCV) infection&#xD;
&#xD;
          -  Liver biopsy consistent with active HCV infection obtained within the last 12 months&#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 (Group 1, 2, 4 and 5) and non-genotype 1 (Group 3)&#xD;
&#xD;
          -  HCV load greater than 50,000 copies messenger ribonucleic acid (mRNA) per ml serum at&#xD;
             screening&#xD;
&#xD;
          -  For Group 5 only: Histology showing moderate or severe fibrosis (portal fibrosis,&#xD;
             septae, periportal and porto-central septae), no regenerative nodes and no incomplete&#xD;
             or complete cirrhosis, corresponding to Ishak score 3 or 4, or Metavir F2 or F3 (if&#xD;
             Ishak is not 5)&#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 patients less&#xD;
             than 3 months after operation or without a negative serum pregnancy test&#xD;
&#xD;
          -  Males not using an adequate form of contraception (condom, sterilisation at least 6&#xD;
             months post operation) if their partner is of childbearing potential (criteria see&#xD;
             above) and is not using an adequate form of contraception (hormonal contraceptives,&#xD;
             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;
          -  Ascites or other current evidence of portal hypertension&#xD;
&#xD;
          -  Histology showing signs of bridging or higher grade fibrosis (e.g. Fibrosis &gt;= Grade 3&#xD;
             (Ishak score) or &gt;= 2 (Metavir score) for treatment groups 1, 2, 3, 4 or for Treatment&#xD;
             group 5: Histology showing less than moderate or severe fibrosis (portal fibrosis,&#xD;
             septae, periportal and porto-central septae), or showing regenerative nodes or&#xD;
             incomplete or complete cirrhosis, corresponding to other Ishak scores than 3 or 4 and&#xD;
             to other Metavir scores than F2 or F3 (or F3 and Ishak 5)&#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)&#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 randomization into this trial&#xD;
&#xD;
          -  Child´s B or C liver diseases at screening (treatment groups 1, 2, 3, 4). Applicable&#xD;
             for treatment group 5 only:&#xD;
&#xD;
               -  For Bilirubin - refer to following exclusion criterion&#xD;
&#xD;
               -  Quick (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 (AP)&#xD;
             exceeding 1.5 x upper limit of normal (ULN) at screening (treatment groups 1, 2, 3,&#xD;
             4). Treatment group 5 (BILN 2061 ZW, 200 mg bid/2 days in patients with advanced liver&#xD;
             fibrosis): Clinically apparent jaundice or a bilirubin &gt;= 2.0 mg/dl at screening.&#xD;
             Increased alkaline phosphatase (AP) is allowed.&#xD;
&#xD;
          -  ALT or AST &gt; 5 x ULN at screening (treatment groups 1, 2, 3, 4). Treatment group 5:&#xD;
             ALT or AST &gt;= 10 x ULN at screening&#xD;
&#xD;
          -  A platelet count of less than 100.000 platelets per mm3 at screening&#xD;
&#xD;
          -  White blood cell count of less than 2,000 cells per mm3 at screening&#xD;
&#xD;
          -  Positive test for human immunodeficiency Virus (HIV) at screening&#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>Virus Diseases</mesh_term>
    <mesh_term>Hepatitis</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/NCT02226952
org study id: 605.5
nct id: NCT02226952
lead sponsor: 
Study to assess the antiviral efficacy, pharmacokinetics and tolerability of BILN 2061 ZW in
      a polyethyleneglycol 400 (PEG 400: ethanol) drinking solution given for two days bid in
      patients with chronic Hepatitis C Virus (HCV) infection.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double
measure: Virus load (VL) 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 clinically relevant changes in alanine aminotransferase (ALT)
time frame: up to day 14
measure: Number of patients with clinically relevant changes in aspartate aminotransferase (AST)
time frame: up to day 14
measure: Number of patients with clinically relevant changes in vital signs
time frame: up to day 14
description: pulse rate, systolic and diastolic blood pressure
measure: Number of patients with clinically relevant changes in electrocardiography (ECG)
time frame: up to day 14
measure: Number of patients with clinically relevant 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: Group 1
arm group type: Experimental
description: BILN 2061 W, medium dose, in patients with genotype 1, minimal fibrosis
arm group label: Group 2
arm group type: Experimental
description: BILN 2061 W, high dose, in patients with genotype 1, minimal fibrosis
arm group label: Group 3
arm group type: Experimental
description: BILN 2061 W, high dose, in non-genotype 1 patients, minimal fibrosis
arm group label: Group 4
arm group type: Experimental
description: BILN 2061 W, low dose, in patients with genotype 1, minimal fibrosis
arm group label: Group 5
arm group type: Experimental
description: BILN 2061 W, medium dose, in patients with genotype 1, advanced fibrosis
arm group label: Placebo
arm group type: Placebo Comparator
intervention type: Drug
intervention name: BILN 2061 W, low dose
arm group label: Group 4
intervention type: Drug
intervention name: BILN 2061 W, medium dose
arm group label: Group 1
arm group label: Group 5
intervention type: Drug
intervention name: BILN 2061 W, high dose
arm group label: Group 2
arm group label: Group 3
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: Virus Diseases
mesh term: Hepatitis