<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/NCT02200029</url>
  </required_header>
  <id_info>
    <org_study_id>M14-168</org_study_id>
    <nct_id>NCT02200029</nct_id>
  </id_info>
  <brief_title>Study With Heptral in Subjects With Liver Disease Due to Alcohol Consumption</brief_title>
  <official_title>Open-Label Study With Ademetionine (Heptral®) in Subjects With Intrahepatic Cholestasis (IHC) Associated With Alcoholic Liver Disease (ALD)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Abbott</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Ascent</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Datamap</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>ClinIntel</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Catalent</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Abbott</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      A research study of an approved drug called Heptral®, ademetionine, to treat adults with&#xD;
      intrahepatic cholestasis (a condition where bile cannot flow from the liver to the duodenum)&#xD;
      in pre-cirrhotic and cirrhotic states. Experience from clinical studies in subjects with&#xD;
      liver disease has shown that ademetionine is effective.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>June 2014</start_date>
  <completion_date type="Actual">February 2015</completion_date>
  <primary_completion_date type="Actual">February 2015</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Concentrations (Units per liter) of Alkaline phosphatase (ALP) or gamma-glutamyltransferase (γGT)</measure>
    <time_frame>from baseline up to the end of treatment visit (56-60 days)</time_frame>
    <description>Improvement of ALP or γGT after 8 weeks of treatment with ademetionine compared to baseline</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Concentrations of ALP, γGT, Alanine Transaminase (ALT) and Aspartate aminotransferase (AST) (Units per liter) and of serum total and conjugated bilirubin (µmol per liter)</measure>
    <time_frame>At baseline and after 2 weeks intravenously (IV) treatment or after 4 weeks oral treatment and after 2 months treatment</time_frame>
    <description>Improvement of ALP, γGT and serum total and conjugated bilirubin, ALT and AST compared to baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The intensity of clinical symptoms (jaundice, pruritus, fatigue and depressed mood) will be recorded for each symptom separately using six categories: No symptoms (0), minimum (1) to maximum (5).</measure>
    <time_frame>At baseline and after 2 weeks IV treatment or after 4 weeks oral treatment and after 2 months treatment</time_frame>
    <description>Record of intensity of jaundice, pruritus, fatigue and depressed mood compared to baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of the responder rate by comparing concentrations at certain time points (units per liter) to baseline concentrations</measure>
    <time_frame>At baseline and after 2 weeks IV treatment or after 4 weeks oral treatment and after 2 months treatment</time_frame>
    <description>&gt;20% reduction of ALP or γGT or normalization of ALP or γGT compared to baseline</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">75</enrollment>
  <condition>Intrahepatic Cholestasis Associated With Alcoholic Liver Disease</condition>
  <arm_group>
    <arm_group_label>Ademetionine IV</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Ademetionine oral</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ademetionine IV+tablet</intervention_name>
    <description>IV ademetionine (500 mg/vial) for 2 weeks followed by oral ademetionine (500 mg/tablet, 2 in the morning and 1 before dinner) for 6 weeks</description>
    <arm_group_label>Ademetionine IV</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ademetionine tablet</intervention_name>
    <description>oral ademetionine (500 mg/tablet, 2 in the morning and 1 before dinner) for 8 weeks</description>
    <arm_group_label>Ademetionine oral</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          -  Signed informed consent given by the subject&#xD;
&#xD;
          -  Age ≥ 18 years to 75 years&#xD;
&#xD;
          -  Chronic liver disease due to alcoholic liver disease&#xD;
&#xD;
          -  Compensated alcoholic liver disease, defined as having a Maddrey Score &lt; 32 and not&#xD;
             being treated with pentoxifylline or prednisolone within 6 months prior to the study&#xD;
&#xD;
          -  History of chronic alcohol use, defined as, history of consumption of &gt; 40 g of&#xD;
             alcohol per day for females and &gt; 80 g alcohol per day for males for more than 5 years&#xD;
             prior to enrolment&#xD;
&#xD;
          -  Subjects who abstain from alcohol for more than 2 weeks and will not consume alcohol&#xD;
             during the study&#xD;
&#xD;
          -  Subjects with Intrahepatic Cholestasis (IHC):&#xD;
&#xD;
          -  ALP: more than 1.5 x upper normal limit and&#xD;
&#xD;
          -  γGT: more than 3 x upper normal limit&#xD;
&#xD;
          -  Subjects with additional serum conjugated bilirubin (SCB) &gt; Upper Limit of Normal&#xD;
             (ULN) will be selected for initial IV treatment&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects with a known hypersensitivity to the active substance of ademetionine or to&#xD;
             any of the inactive ingredients&#xD;
&#xD;
          -  Subjects with extrahepatic cause of cholestasis (proven by ultrasound or described in&#xD;
             medical history)&#xD;
&#xD;
          -  Diagnosis of human immunodeficiency virus (HIV) in medical history&#xD;
&#xD;
          -  Subjects with chronic liver disease Child-Pugh class C&#xD;
&#xD;
          -  Subjects in the decompensation stage of ALD (such as Maddrey Score &gt;32)&#xD;
&#xD;
          -  Subjects with primary sclerosing cholangitis (PSC)&#xD;
&#xD;
          -  Subjects with primary biliary cirrhosis (PBC)&#xD;
&#xD;
          -  Any form of malignancy within the past 5 years and/or basal cell carcinoma and&#xD;
             squamous cell carcinoma of the skin within the past two years&#xD;
&#xD;
          -  Subjects with drug-induced liver disease&#xD;
&#xD;
          -  History of active substance abuse (oral, inhaled or injected) within one year prior to&#xD;
             the study&#xD;
&#xD;
          -  Subjects with renal impairment (creatinine level of &gt;2.0 mg/dL or &gt; 150 µmol/l)&#xD;
&#xD;
          -  Subjects with known genetic defects affecting the methionine cycle and/or causing&#xD;
             homocystinuria and/or hyperhomocysteinemia (e.g., cystathionine beta-synthase&#xD;
             deficiency, Vitamin B12 metabolism defect) or known folate, Vitamin B6 or B12&#xD;
             deficiency&#xD;
&#xD;
          -  Subjects on total parenteral nutrition in the year prior to screening&#xD;
&#xD;
          -  Subjects after or planned for bariatric surgery (jejunoileal bypass or gastric weight&#xD;
             loss surgery)&#xD;
&#xD;
          -  Subjects after liver transplantation and subjects on the waiting list for liver&#xD;
             transplantation&#xD;
&#xD;
          -  Subjects with any of the following disease in medical history:&#xD;
&#xD;
          -  Viral hepatitis (serum positive HBcAb or Hepatitis C Virus (HCV) RNA)&#xD;
&#xD;
          -  Evidence of autoimmune liver disease&#xD;
&#xD;
          -  Wilson´s disease&#xD;
&#xD;
          -  Hemochromatosis&#xD;
&#xD;
          -  Alpha-1-antitrypsin deficiency&#xD;
&#xD;
          -  Subjects with history of biliary diversion&#xD;
&#xD;
          -  History of major depression or bipolar disease&#xD;
&#xD;
          -  Women of childbearing potential: positive urine pregnancy test during screening or&#xD;
             unwillingness to use an effective form of birth control during the study.&#xD;
&#xD;
          -  Breastfeeding women&#xD;
&#xD;
          -  Any condition that, in the opinion of the investigator, does not justify the patient's&#xD;
             inclusion into the study&#xD;
&#xD;
          -  Investigational drug intake within one month prior to the study&#xD;
&#xD;
          -  Active, serious medical disease other than ALD with likely life-expectancy less than&#xD;
             five years&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Suntje Sander-Struckmeier, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Abbott</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Research facility ORG-000962</name>
      <address>
        <city>Moscow</city>
        <zip>107014</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research facility ORG-000957</name>
      <address>
        <city>Moscow</city>
        <zip>117292</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research facility ORG-000961</name>
      <address>
        <city>Moscow</city>
        <zip>119435</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research facility ID ORG-000960</name>
      <address>
        <city>Moscow</city>
        <zip>119992</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research facility ID ORG-000726</name>
      <address>
        <city>Moscow</city>
        <zip>125284</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research facility ORG-000967</name>
      <address>
        <city>St. Petersburg</city>
        <zip>117630</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research facility ORG-000966</name>
      <address>
        <city>St. Petersburg</city>
        <zip>191015</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research facility ORG-000968</name>
      <address>
        <city>St. Petersburg</city>
        <zip>195257</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research facility ORG-000965</name>
      <address>
        <city>St. Petersburg</city>
        <zip>197022</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research facility ORG-000970</name>
      <address>
        <city>St. Petersburg</city>
        <zip>198216</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research facility ORG-000958</name>
      <address>
        <city>Troitsk</city>
        <zip>142190</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research facility ORG-000969</name>
      <address>
        <city>Yaroslavl</city>
        <zip>150003</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Russian Federation</country>
  </location_countries>
  <verification_date>June 2015</verification_date>
  <study_first_submitted>July 21, 2014</study_first_submitted>
  <study_first_submitted_qc>July 24, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 25, 2014</study_first_posted>
  <last_update_submitted>June 15, 2015</last_update_submitted>
  <last_update_submitted_qc>June 15, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">June 16, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Intrahepatic Cholestasis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Liver Diseases</mesh_term>
    <mesh_term>Cholestasis</mesh_term>
    <mesh_term>Liver Diseases, Alcoholic</mesh_term>
    <mesh_term>Cholestasis, Intrahepatic</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/NCT02200029
org study id: M14-168
nct id: NCT02200029
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
A research study of an approved drug called Heptral®, ademetionine, to treat adults with
      intrahepatic cholestasis (a condition where bile cannot flow from the liver to the duodenum)
      in pre-cirrhotic and cirrhotic states. Experience from clinical studies in subjects with
      liver disease has shown that ademetionine is effective.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Concentrations (Units per liter) of Alkaline phosphatase (ALP) or gamma-glutamyltransferase (γGT)
time frame: from baseline up to the end of treatment visit (56-60 days)
description: Improvement of ALP or γGT after 8 weeks of treatment with ademetionine compared to baseline
measure: Concentrations of ALP, γGT, Alanine Transaminase (ALT) and Aspartate aminotransferase (AST) (Units per liter) and of serum total and conjugated bilirubin (µmol per liter)
time frame: At baseline and after 2 weeks intravenously (IV) treatment or after 4 weeks oral treatment and after 2 months treatment
description: Improvement of ALP, γGT and serum total and conjugated bilirubin, ALT and AST compared to baseline
measure: The intensity of clinical symptoms (jaundice, pruritus, fatigue and depressed mood) will be recorded for each symptom separately using six categories: No symptoms (0), minimum (1) to maximum (5).
time frame: At baseline and after 2 weeks IV treatment or after 4 weeks oral treatment and after 2 months treatment
description: Record of intensity of jaundice, pruritus, fatigue and depressed mood compared to baseline
measure: Evaluation of the responder rate by comparing concentrations at certain time points (units per liter) to baseline concentrations
time frame: At baseline and after 2 weeks IV treatment or after 4 weeks oral treatment and after 2 months treatment
description: >20% reduction of ALP or γGT or normalization of ALP or γGT compared to baseline
arm group label: Ademetionine IV
arm group type: Experimental
arm group label: Ademetionine oral
arm group type: Experimental
intervention type: Drug
intervention name: Ademetionine IV+tablet
description: IV ademetionine (500 mg/vial) for 2 weeks followed by oral ademetionine (500 mg/tablet, 2 in the morning and 1 before dinner) for 6 weeks
arm group label: Ademetionine IV
intervention type: Drug
intervention name: Ademetionine tablet
description: oral ademetionine (500 mg/tablet, 2 in the morning and 1 before dinner) for 8 weeks
arm group label: Ademetionine oral
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Suntje Sander-Struckmeier, PhD
role: Study Director
affiliation: Abbott
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Russian Federation
responsible party type: Sponsor
mesh term: Liver Diseases
mesh term: Cholestasis
mesh term: Liver Diseases, Alcoholic
mesh term: Cholestasis, Intrahepatic