<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/NCT02197598</url>
  </required_header>
  <id_info>
    <org_study_id>15871A</org_study_id>
    <secondary_id>2014-000413-31</secondary_id>
    <nct_id>NCT02197598</nct_id>
  </id_info>
  <brief_title>Treatment of Patients Suffering of Alcohol Dependence and Impaired Liver Function With Selincro® As-needed Use</brief_title>
  <official_title>Exploratory, Interventional, Open-label, Fixed-dose Study With Selincro® As-needed Use, in Alcohol Dependent Patients With Liver Impairment</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>H. Lundbeck A/S</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>H. Lundbeck A/S</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to explore the treatment effects of Selincro in alcohol&#xD;
      dependent patients with liver impairment.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>September 2014</start_date>
  <primary_completion_date type="Actual">December 2015</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change from baseline in the number of heavy drinking days per month (HDDs) (days/month)</measure>
    <time_frame>Baseline to months 1, 2 and 3</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline in the number of HDDs per week (days/week)</measure>
    <time_frame>Baseline to weeks 1 and 2</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline in total alcohol consumption (TAC) (g alcohol/day)</measure>
    <time_frame>Baseline to months 1, 2 and 3</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline in TAC (g alcohol/day)</measure>
    <time_frame>Baseline to weeks 1 and 2</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Response Shift Drinking Risk Level (RSDRL)</measure>
    <time_frame>Baseline to month 3</time_frame>
    <description>Defined as a downward shift from baseline in drinking risk level (DRL); for patients with a very high DRL at baseline, a shift to medium DRL or lower; for patients with a high DRL at baseline, a shift to low DRL or below</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Response Low Drinking Risk Level (RLDRL)</measure>
    <time_frame>Baseline to month 3</time_frame>
    <description>Defined as a downward shift from baseline in DRL to low DRL or below</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Response defined as ≥70% reduction in TAC</measure>
    <time_frame>Baseline to month 3</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Response defined as 0 to 4 HDDs (days/month)</measure>
    <time_frame>Month 3</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Clinical Global Impression, global improvement (CGI-I).</measure>
    <time_frame>Weeks 4 and 12</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline in Clinical Global Impression, Severity of illness (CGI-S)</measure>
    <time_frame>Baseline to weeks 4 and 12</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in the Short-Form 36-Item Health Survey (SF-36)</measure>
    <time_frame>Baseline to week 12</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in liver stiffness</measure>
    <time_frame>Baseline to weeks 1,2 4 and 12</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Category shift in fibrosis stage</measure>
    <time_frame>Baseline to weeks 1,2 4, and 12</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in transaminases and γ-glutamyl transferase (γGT)</measure>
    <time_frame>Baseline to weeks 1,2,4,8, and 12</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in bilirubin, albumin, and International Normalized Ratio (INR)</measure>
    <time_frame>Baseline to weeks 1,2,4,8, and 12</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of adverse events</measure>
    <time_frame>Screening to week 14</time_frame>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">45</enrollment>
  <condition>Alcohol Dependence</condition>
  <arm_group>
    <arm_group_label>Selincro® (nalmefene) 18 mg, tablets</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>One tablet orally for 12 weeks on days when the patient perceives a risk of drinking alcohol, preferably 1-2 hours prior to the anticipated risk of drinking.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>nalmefene</intervention_name>
    <arm_group_label>Selincro® (nalmefene) 18 mg, tablets</arm_group_label>
    <other_name>Selincro®</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  The patient has alcohol dependence, diagnosed at screening according to DSM-IV-TR™&#xD;
&#xD;
          -  The patient has had an average alcohol consumption at, at least, a high drinking risk&#xD;
             level (that is &gt;60 g of alcohol/day for men and &gt;40 g of alcohol/day for women) in the&#xD;
             4 weeks preceding the Screening Visit and in the period between the Screening and&#xD;
             Inclusion Visits (that is, in the Screening Period)&#xD;
&#xD;
          -  The patient has liver impairment defined by elevated liver stiffness and elevated&#xD;
             liver enzymes at the Screening Visit (both criteria have to be fulfilled): liver&#xD;
             stiffness (LS) as measured by Fibroscan &gt;6 kPa, elevated transaminases (AST or ALT).&#xD;
             Transaminase levels up to 5 times the upper limit of the reference range and γGT&#xD;
             levels up to 10 times the upper limit of the reference range are allowed. At the&#xD;
             discretion of the investigator, transaminase levels &gt;5 times the upper limit of the&#xD;
             reference range and γGT &gt;10 times the upper limit of the reference range can be&#xD;
             allowed if considered habitual for the patient, either confirmed by patient records or&#xD;
             a repeat measurement during the Screening Period&#xD;
&#xD;
          -  The patient has a breath alcohol concentration (BrAC) &lt;0.02% at the Screening Visit.&#xD;
&#xD;
          -  The patient provides a stable address and telephone number&#xD;
&#xD;
          -  The patient is a man or woman, aged ≥ 18 years&#xD;
&#xD;
          -  The patient has BMI≤30 kg/m2&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  The patient has any psychiatric disorder or Axis I disorder (DSM-IV-TR™ criteria),&#xD;
             established as the primary diagnosis, other than alcohol dependence assessed using the&#xD;
             Mini International Neuropsychiatric Interview (MINI) or another diagnostic interview ,&#xD;
             that in any way will interfere with the ability of the patient to take part in the&#xD;
             study&#xD;
&#xD;
          -  The patient has reported current use of, or has been tested positive for, drugs of&#xD;
             abuse (opiates, methadone, cocaine, amphetamines [including ecstasy], barbiturates)&#xD;
&#xD;
          -  The patient has severe liver impairment classified with a Child-Pugh Score C&#xD;
&#xD;
          -  The patient has one or more clinical laboratory test values outside the reference&#xD;
             range, based on the blood and urine samples taken at the Screening Visit, that are of&#xD;
             potential risk to the patient's safety, or the patient has: Severe renal impairment&#xD;
             (eGFR &lt;30 mL/min per 1.73 m2), and/or Hypercholesterolemia with serum cholesterol&#xD;
             levels &gt; 300 mg/dL, (&gt;7,758 mmol/L), and/or bilirubin &gt; 3 mg/dL (50 μmol/L)&#xD;
&#xD;
          -  The patient has had &lt;6 heavy drinking days (HDDs, defined by the European Medicines&#xD;
             Agency as a day with an alcohol consumption &gt;60 g for men or &gt;40 g for women) in the 4&#xD;
             weeks preceding the Screening Visit&#xD;
&#xD;
          -  The patient has &gt;5 consecutive abstinence days in the 4 weeks preceding the Screening&#xD;
             Visit&#xD;
&#xD;
          -  The patient has a recent history of acute alcohol withdrawal syndrome (including&#xD;
             hallucinations, seizures, or delirium tremens)&#xD;
&#xD;
        Other protocol-defined inclusion and exclusion criteria may apply.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Email contact via H.Lundbeck A/S</last_name>
    <role>Study Director</role>
    <affiliation>LundbeckClinicalTrials@lundbeck.com</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>DE001</name>
      <address>
        <city>Heidelberg</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>DE002</name>
      <address>
        <city>Mannheim</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Optuminisight</name>
      <address>
        <city>München</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>December 2016</verification_date>
  <study_first_submitted>July 21, 2014</study_first_submitted>
  <study_first_submitted_qc>July 21, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 22, 2014</study_first_posted>
  <last_update_submitted>December 13, 2016</last_update_submitted>
  <last_update_submitted_qc>December 13, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 14, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>nalmefene, alcohol consumption, liver effects</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Alcoholism</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Nalmefene</mesh_term>
  </intervention_browse>
  <study_docs>
    <study_doc>
      <doc_id>2014-000413-31</doc_id>
      <doc_type>EMA EudraCT Results</doc_type>
      <doc_url>https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-000413-31/results</doc_url>
    </study_doc>
  </study_docs>
  <!-- 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/NCT02197598
org study id: 15871A
secondary id: 2014-000413-31
nct id: NCT02197598
lead sponsor: 
has dmc: No
The purpose of this study is to explore the treatment effects of Selincro in alcohol
      dependent patients with liver impairment.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change from baseline in the number of heavy drinking days per month (HDDs) (days/month)
time frame: Baseline to months 1, 2 and 3
measure: Change from baseline in the number of HDDs per week (days/week)
time frame: Baseline to weeks 1 and 2
measure: Change from baseline in total alcohol consumption (TAC) (g alcohol/day)
time frame: Baseline to months 1, 2 and 3
measure: Change from baseline in TAC (g alcohol/day)
time frame: Baseline to weeks 1 and 2
measure: Response Shift Drinking Risk Level (RSDRL)
time frame: Baseline to month 3
description: Defined as a downward shift from baseline in drinking risk level (DRL); for patients with a very high DRL at baseline, a shift to medium DRL or lower; for patients with a high DRL at baseline, a shift to low DRL or below
measure: Response Low Drinking Risk Level (RLDRL)
time frame: Baseline to month 3
description: Defined as a downward shift from baseline in DRL to low DRL or below
measure: Response defined as ≥70% reduction in TAC
time frame: Baseline to month 3
measure: Response defined as 0 to 4 HDDs (days/month)
time frame: Month 3
measure: Clinical Global Impression, global improvement (CGI-I).
time frame: Weeks 4 and 12
measure: Change from baseline in Clinical Global Impression, Severity of illness (CGI-S)
time frame: Baseline to weeks 4 and 12
measure: Change in the Short-Form 36-Item Health Survey (SF-36)
time frame: Baseline to week 12
measure: Change in liver stiffness
time frame: Baseline to weeks 1,2 4 and 12
measure: Category shift in fibrosis stage
time frame: Baseline to weeks 1,2 4, and 12
measure: Change in transaminases and γ-glutamyl transferase (γGT)
time frame: Baseline to weeks 1,2,4,8, and 12
measure: Change in bilirubin, albumin, and International Normalized Ratio (INR)
time frame: Baseline to weeks 1,2,4,8, and 12
measure: Number of adverse events
time frame: Screening to week 14
arm group label: Selincro® (nalmefene) 18 mg, tablets
arm group type: Experimental
description: One tablet orally for 12 weeks on days when the patient perceives a risk of drinking alcohol, preferably 1-2 hours prior to the anticipated risk of drinking.
intervention type: Drug
intervention name: nalmefene
arm group label: Selincro® (nalmefene) 18 mg, tablets
other name: Selincro®
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Email contact via H.Lundbeck A/S
role: Study Director
affiliation: LundbeckClinicalTrials@lundbeck.com
facility: 
facility: 
facility: 
country: Germany
responsible party type: Sponsor
mesh term: Alcoholism
mesh term: Nalmefene
study doc: 