<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/NCT02252536</url>
  </required_header>
  <id_info>
    <org_study_id>NCIG - 006</org_study_id>
    <nct_id>NCT02252536</nct_id>
  </id_info>
  <brief_title>HORIZANT (Gabapentin Enacarbil Extended-Release Tablets) for the Treatment of Alcohol Use Disorder</brief_title>
  <official_title>Randomized, Double Blind, Placebo-Controlled Trial of the Safety and Efficacy of HORIZANT (Gabapentin Enacarbil) Extended-Release Tablets for the Treatment of Alcohol Use Disorder</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Institute on Alcohol Abuse and Alcoholism (NIAAA)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Arbor Pharmaceuticals, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>National Institute on Alcohol Abuse and Alcoholism (NIAAA)</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine whether gabapentin enacarbil is effective in the&#xD;
      treatment of problems with alcohol.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>June 2015</start_date>
  <completion_date type="Actual">March 2017</completion_date>
  <primary_completion_date type="Actual">March 2017</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of Subjects With no Heavy Drinking Days (PSNHDD)</measure>
    <time_frame>Weeks 22-25</time_frame>
    <description>The primary objective of the study is to compare the efficacy of HORIZANT (gabapentin enacarbil) Extended-Release Tablets 600 mg twice daily (BID) with matched placebo on the primary alcohol consumption outcome endpoint, percentage of subjects with no heavy drinking days (PSNHDD) during the last 4 weeks of treatment, among patients with Alcohol Use Disorder (AUD).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Subjects Abstinent From Alcohol (Key Secondary Endpoint)</measure>
    <time_frame>Weeks 22-25</time_frame>
    <description>Timeline Follow-back drinking data is used to calculate the % of subjects that report not drinking alcohol during weeks 22-25</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Subjects With a World Health Organization (WHO) Drinking Risk Category Decrease of at Least 1-level</measure>
    <time_frame>Weeks 22-25</time_frame>
    <description>Timeline Follow Back data is used to calculate the % of participants that decrease at least 1-level WHO drinking risk category. The WHO has developed a drinking risk categorical scale that can be used in a responder analysis approach to assess clinically relevant decreases in alcohol consumption (Aubin et al-2015). The WHO 1- and 2-level decrease endpoints are the percentage of subjects experiencing at least 1- and 2-level decrease in WHO levels of alcohol consumption, respectively, from the level at baseline (the period including the 28 days before screening) to the level during the last 4 weeks of the maintenance phase (Study Weeks 22-25). The WHO levels are as follows:&#xD;
Males Females Low Risk 1 to 40g 1 to 20g Medium Risk 41 to 60g 21 to 40g High Risk 61 to 100g 41 to 60g Very High Risk 101+g 61+g</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Subjects With a World Health Organization (WHO) Drinking Risk Category Decrease of at Least 2-levels</measure>
    <time_frame>Weeks 22-25</time_frame>
    <description>Timeline Follow Back data is used to calculate the % of participants that decrease at least 1-level WHO drinking risk category. The WHO has developed a drinking risk categorical scale that can be used in a responder analysis approach to assess clinically relevant decreases in alcohol consumption (Aubin et al-2015). The WHO 1- and 2-level decrease endpoints are the percentage of subjects experiencing at least 1- and 2-level decrease in WHO levels of alcohol consumption, respectively, from the level at baseline (the period including the 28 days before screening) to the level during the last 4 weeks of the maintenance phase (Study Weeks 22-25). The WHO levels are as follows:&#xD;
Males Females Low Risk 1 to 40g 1 to 20g Medium Risk 41 to 60g 21 to 40g High Risk 61 to 100g 41 to 60g Very High Risk 101+g 61+g</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Days Abstinent Per Week</measure>
    <time_frame>Weeks 22-25</time_frame>
    <description>Timeline Follow Back daily drinking data used to calculate the % of days abstinent per week.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Heavy Drinking Days Per Week</measure>
    <time_frame>Weeks 22-25</time_frame>
    <description>Timeline Follow Back data used to calculate the % of heavy drinking days per week. Heavy drinking is 4+ drinks per day for females and 5+ drinks per day for males</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Weekly Mean Number of Drinks Per Week</measure>
    <time_frame>Weeks 22-25</time_frame>
    <description>Timeline Follow Back data used to calculate the weekly mean number of drinks per week</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Weekly Mean Drinks Per Drinking Day</measure>
    <time_frame>Weeks 22-25</time_frame>
    <description>Timeline Follow Back daily drinking data used to calculate the weekly mean drinks per drinking day</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cigarettes Per Week Among Smokers</measure>
    <time_frame>Weeks 22-25</time_frame>
    <description>A quantity frequency interview of three questions to assess cigarette smoking behavior and other tobacco/nicotine containing products use during the study: 1) &quot;Over the past week, on how many days did you smoke cigarettes?&quot;, 2) &quot;On the days you smoked during the past week, how many cigarettes did you smoke on average?&quot;, and 3) &quot;Have you used any other tobacco or nicotine containing products besides cigarettes in the past week (e.g., cigars, cigarellos, pipes, bidis, or smokeless tobacco such as pan, chewing tobacco, or snuff, or nicotine replacement therapies such as patch or gum)?&quot;.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Alcohol Craving Score [Alcohol Craving Scale - Short Form (ACQ-SR-R)]</measure>
    <time_frame>Weeks 24 and 26</time_frame>
    <description>The ACQ-SR-R contains 12-items adapted from the 47-item ACQ-NOW developed by Singleton et al (1994) to assess craving for alcohol among alcohol users in the current context (right now). Each item has a 1 to 7 raw score (from strongly disagree to strongly agree). Items 3, 8, and 11 are reverse keyed. A general craving index is derived by summing all items and dividing by 12. Minimum score is 1 and maximum score is 7. Higher scores are indicative of higher craving.&#xD;
Mixed effects models as stated in Section 9.4.3 of the SAP will be generated for the total score and for the 4 subscales. Covariates for these models will be identified</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Alcohol Related Consequences (ImBIBe) Score</measure>
    <time_frame>Weeks 24 and 26</time_frame>
    <description>ImBIBe is a 15-item questionnaire in which the subject responds on a 5-point scale (0-4) responses to questions on the consequences of alcohol use. This scale was adapted from the Drinker Inventory of Consequences questionnaire based on FDA recommendations on patient reported outcomes (Miller &amp; Tonigen-1995). The potential range is 0-60. A higher score indicates a worse outcome. The questions are added together. A question that is missing is imputed with the average value of all other questions in the questionnaire.The total score is the sum of the individual item scores.&#xD;
Mixed effects models as stated in Section 9.4.3 will be generated for the total score. Covariates for these models will be identified</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pittsburgh Sleep Quality Index (PSQI) Score</measure>
    <time_frame>Week 26</time_frame>
    <description>The PSQI is a 19-item questionnaire assessing the subject's overall sleep experience in the past 30 days (Buysse et al-1989). The lower the overall score, the better the person sleeps. The tool has an adequate internal reliability, validity and consistency for clinical and community samples of the various populations. Range is (0-21); &gt;6 indicative of &quot;poor&quot; sleep quality.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Beck Anxiety Inventory (BAI) Score</measure>
    <time_frame>Week 26</time_frame>
    <description>The BAI consists of 21 questions about how the subject has been feeling in the last week, expressed as common symptoms of anxiety (such as numbness and tingling, sweating not due to heat, and fear of the worst happening). This inventory was designed to minimize the overlap with depression scales (Beck et al-1988).The BAI has a maximum score of 63. The standardized cutoffs for anxiety severity are: 0-7: minimal level of anxiety 8-15: mild anxiety 16-25: moderate anxiety 26-63: severe anxiety</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Beck Depression Inventory - II</measure>
    <time_frame>Week 26</time_frame>
    <description>The BDI-II is a 21-item multiple choice questionnaire that is used for measuring the severity of depression (Beck et al-1966). Each item is scored on a scale value of 0 to 3. The standardized cutoffs for depression severity are:&#xD;
0-13: minimal depression 14-19: mild depression 20-28: moderate depression 29-63: severe depression</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">346</enrollment>
  <condition>Alcohol Use Disorder</condition>
  <arm_group>
    <arm_group_label>Sugar Pill</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Matching placebo, sugar pill</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Gabapentin Enacarbil</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>600 mg Gabapentin Enacarbil (Horizant)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>gabapentin enacarbil</intervention_name>
    <description>Horizant Extended Release Tablets, 600 mg, white to off-white, oval shaped tablets, taken 2 times per day</description>
    <arm_group_label>Gabapentin Enacarbil</arm_group_label>
    <other_name>Horizant Extended Release Tablets</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo tablet, white to off-white, oval shaped tablets, taken 2 times per day</description>
    <arm_group_label>Sugar Pill</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Subjects must meet each one of the following inclusion criteria in order to be eligible for&#xD;
        participation in the study:&#xD;
&#xD;
          1. Be at least 21 years of age.&#xD;
&#xD;
          2. Have a current (past 12 months) DSM-5 diagnosis of AUD.&#xD;
&#xD;
          3. Have a BAC by breathalyzer equal to 0.000 when s/he signed the informed consent&#xD;
             document (either just prior to or immediately after signing consent).&#xD;
&#xD;
          4. Be seeking treatment for problems with alcohol.&#xD;
&#xD;
        Additional will be evaluated in clinic.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Evaluations will be conducted in clinic.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Raye Z. Litten, Ph.D.</last_name>
    <role>Study Chair</role>
    <affiliation>National Institute on Alcohol Abuse and Alcoholism (NIAAA)</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of California Los Angeles</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Friends Research Institute</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Miami, Miller School of Medicine</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33136</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Johns Hopkins University School of Medicine</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21224</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Boston University Medical Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02118</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dartmouth-Hitchcock Medical Center</name>
      <address>
        <city>Lebanon</city>
        <state>New Hampshire</state>
        <zip>03756</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mount Sinai St. Luke's Hospital</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10025</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Pennsylvania</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The University of Texas Southwestern Medical Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75235</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Virginia</name>
      <address>
        <city>Charlottesville</city>
        <state>Virginia</state>
        <zip>22911</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2018</verification_date>
  <study_first_submitted>September 26, 2014</study_first_submitted>
  <study_first_submitted_qc>September 26, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 30, 2014</study_first_posted>
  <results_first_submitted>April 9, 2018</results_first_submitted>
  <results_first_submitted_qc>August 20, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">September 21, 2018</results_first_posted>
  <last_update_submitted>October 15, 2018</last_update_submitted>
  <last_update_submitted_qc>October 15, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">November 14, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>alcohol use disorder</keyword>
  <keyword>alcoholism</keyword>
  <keyword>alcohol dependence</keyword>
  <keyword>drinking alcohol</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Alcoholism</mesh_term>
    <mesh_term>Alcohol Drinking</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Gabapentin</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>August 18, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/36/NCT02252536/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>August 22, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/36/NCT02252536/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>The study was a Phase 2, randomized, double-blind, placebo controlled, parallel-group 26-week treatment clinical trial. Candidates responded by telephone to advertisements at 10 academic sites in the US between June 2015 and February 2017.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Sugar Pill</title>
          <description>Matching placebo, sugar pill&#xD;
Placebo: Placebo tablet, white to off-white, oval shaped tablets, taken 2 times per day</description>
        </group>
        <group group_id="P2">
          <title>Gabapentin Enacarbil</title>
          <description>600 mg Gabapentin Enacarbil (Horizant)&#xD;
gabapentin enacarbil: Horizant Extended Release Tablets, 600 mg, white to off-white, oval shaped tablets, taken 2 times per day</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="173"/>
                <participants group_id="P2" count="173"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="168"/>
                <participants group_id="P2" count="170"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Sugar Pill</title>
          <description>Matching placebo, sugar pill&#xD;
Placebo: Placebo tablet, white to off-white, oval shaped tablets, taken 2 times per day</description>
        </group>
        <group group_id="B2">
          <title>Gabapentin Enacarbil</title>
          <description>600 mg Gabapentin Enacarbil (Horizant)&#xD;
gabapentin enacarbil: Horizant Extended Release Tablets, 600 mg, white to off-white, oval shaped tablets, taken 2 times per day</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="168"/>
            <count group_id="B2" value="170"/>
            <count group_id="B3" value="338"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="49.4" spread="11.4"/>
                    <measurement group_id="B2" value="50.7" spread="10.3"/>
                    <measurement group_id="B3" value="50.1" spread="10.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="67"/>
                    <measurement group_id="B2" value="48"/>
                    <measurement group_id="B3" value="115"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="101"/>
                    <measurement group_id="B2" value="122"/>
                    <measurement group_id="B3" value="223"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="32"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="146"/>
                    <measurement group_id="B2" value="150"/>
                    <measurement group_id="B3" value="296"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="28"/>
                    <measurement group_id="B2" value="35"/>
                    <measurement group_id="B3" value="63"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="126"/>
                    <measurement group_id="B2" value="117"/>
                    <measurement group_id="B3" value="243"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="19"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="168"/>
                    <measurement group_id="B2" value="170"/>
                    <measurement group_id="B3" value="338"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Subjects With no Heavy Drinking Days (PSNHDD)</title>
        <description>The primary objective of the study is to compare the efficacy of HORIZANT (gabapentin enacarbil) Extended-Release Tablets 600 mg twice daily (BID) with matched placebo on the primary alcohol consumption outcome endpoint, percentage of subjects with no heavy drinking days (PSNHDD) during the last 4 weeks of treatment, among patients with Alcohol Use Disorder (AUD).</description>
        <time_frame>Weeks 22-25</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Sugar Pill</title>
            <description>Matching placebo, sugar pill&#xD;
Placebo: Placebo tablet, white to off-white, oval shaped tablets, taken 2 times per day</description>
          </group>
          <group group_id="O2">
            <title>Gabapentin Enacarbil</title>
            <description>600 mg Gabapentin Enacarbil (Horizant)&#xD;
gabapentin enacarbil: Horizant Extended Release Tablets, 600 mg, white to off-white, oval shaped tablets, taken 2 times per day</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Subjects With no Heavy Drinking Days (PSNHDD)</title>
          <description>The primary objective of the study is to compare the efficacy of HORIZANT (gabapentin enacarbil) Extended-Release Tablets 600 mg twice daily (BID) with matched placebo on the primary alcohol consumption outcome endpoint, percentage of subjects with no heavy drinking days (PSNHDD) during the last 4 weeks of treatment, among patients with Alcohol Use Disorder (AUD).</description>
          <units>percentage of subjects with NHDD</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="168"/>
                <count group_id="O2" value="170"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17.3"/>
                    <measurement group_id="O2" value="24.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Subjects Abstinent From Alcohol (Key Secondary Endpoint)</title>
        <description>Timeline Follow-back drinking data is used to calculate the % of subjects that report not drinking alcohol during weeks 22-25</description>
        <time_frame>Weeks 22-25</time_frame>
        <population>no imputation was performed so the number analyzed is reduced</population>
        <group_list>
          <group group_id="O1">
            <title>Sugar Pill</title>
            <description>Matching placebo, sugar pill&#xD;
Placebo: Placebo tablet, white to off-white, oval shaped tablets, taken 2 times per day</description>
          </group>
          <group group_id="O2">
            <title>Gabapentin Enacarbil</title>
            <description>600 mg Gabapentin Enacarbil (Horizant)&#xD;
gabapentin enacarbil: Horizant Extended Release Tablets, 600 mg, white to off-white, oval shaped tablets, taken 2 times per day</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Subjects Abstinent From Alcohol (Key Secondary Endpoint)</title>
          <description>Timeline Follow-back drinking data is used to calculate the % of subjects that report not drinking alcohol during weeks 22-25</description>
          <population>no imputation was performed so the number analyzed is reduced</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="136"/>
                <count group_id="O2" value="146"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16"/>
                    <measurement group_id="O2" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Subjects With a World Health Organization (WHO) Drinking Risk Category Decrease of at Least 1-level</title>
        <description>Timeline Follow Back data is used to calculate the % of participants that decrease at least 1-level WHO drinking risk category. The WHO has developed a drinking risk categorical scale that can be used in a responder analysis approach to assess clinically relevant decreases in alcohol consumption (Aubin et al-2015). The WHO 1- and 2-level decrease endpoints are the percentage of subjects experiencing at least 1- and 2-level decrease in WHO levels of alcohol consumption, respectively, from the level at baseline (the period including the 28 days before screening) to the level during the last 4 weeks of the maintenance phase (Study Weeks 22-25). The WHO levels are as follows:&#xD;
Males Females Low Risk 1 to 40g 1 to 20g Medium Risk 41 to 60g 21 to 40g High Risk 61 to 100g 41 to 60g Very High Risk 101+g 61+g</description>
        <time_frame>Weeks 22-25</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Sugar Pill</title>
            <description>Matching placebo, sugar pill&#xD;
Placebo: Placebo tablet, white to off-white, oval shaped tablets, taken 2 times per day</description>
          </group>
          <group group_id="O2">
            <title>Gabapentin Enacarbil</title>
            <description>600 mg Gabapentin Enacarbil (Horizant)&#xD;
gabapentin enacarbil: Horizant Extended Release Tablets, 600 mg, white to off-white, oval shaped tablets, taken 2 times per day</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Subjects With a World Health Organization (WHO) Drinking Risk Category Decrease of at Least 1-level</title>
          <description>Timeline Follow Back data is used to calculate the % of participants that decrease at least 1-level WHO drinking risk category. The WHO has developed a drinking risk categorical scale that can be used in a responder analysis approach to assess clinically relevant decreases in alcohol consumption (Aubin et al-2015). The WHO 1- and 2-level decrease endpoints are the percentage of subjects experiencing at least 1- and 2-level decrease in WHO levels of alcohol consumption, respectively, from the level at baseline (the period including the 28 days before screening) to the level during the last 4 weeks of the maintenance phase (Study Weeks 22-25). The WHO levels are as follows:&#xD;
Males Females Low Risk 1 to 40g 1 to 20g Medium Risk 41 to 60g 21 to 40g High Risk 61 to 100g 41 to 60g Very High Risk 101+g 61+g</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="134"/>
                <count group_id="O2" value="146"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="107"/>
                    <measurement group_id="O2" value="115"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Subjects With a World Health Organization (WHO) Drinking Risk Category Decrease of at Least 2-levels</title>
        <description>Timeline Follow Back data is used to calculate the % of participants that decrease at least 1-level WHO drinking risk category. The WHO has developed a drinking risk categorical scale that can be used in a responder analysis approach to assess clinically relevant decreases in alcohol consumption (Aubin et al-2015). The WHO 1- and 2-level decrease endpoints are the percentage of subjects experiencing at least 1- and 2-level decrease in WHO levels of alcohol consumption, respectively, from the level at baseline (the period including the 28 days before screening) to the level during the last 4 weeks of the maintenance phase (Study Weeks 22-25). The WHO levels are as follows:&#xD;
Males Females Low Risk 1 to 40g 1 to 20g Medium Risk 41 to 60g 21 to 40g High Risk 61 to 100g 41 to 60g Very High Risk 101+g 61+g</description>
        <time_frame>Weeks 22-25</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Sugar Pill</title>
            <description>Matching placebo, sugar pill&#xD;
Placebo: Placebo tablet, white to off-white, oval shaped tablets, taken 2 times per day</description>
          </group>
          <group group_id="O2">
            <title>Gabapentin Enacarbil</title>
            <description>600 mg Gabapentin Enacarbil (Horizant)&#xD;
gabapentin enacarbil: Horizant Extended Release Tablets, 600 mg, white to off-white, oval shaped tablets, taken 2 times per day</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Subjects With a World Health Organization (WHO) Drinking Risk Category Decrease of at Least 2-levels</title>
          <description>Timeline Follow Back data is used to calculate the % of participants that decrease at least 1-level WHO drinking risk category. The WHO has developed a drinking risk categorical scale that can be used in a responder analysis approach to assess clinically relevant decreases in alcohol consumption (Aubin et al-2015). The WHO 1- and 2-level decrease endpoints are the percentage of subjects experiencing at least 1- and 2-level decrease in WHO levels of alcohol consumption, respectively, from the level at baseline (the period including the 28 days before screening) to the level during the last 4 weeks of the maintenance phase (Study Weeks 22-25). The WHO levels are as follows:&#xD;
Males Females Low Risk 1 to 40g 1 to 20g Medium Risk 41 to 60g 21 to 40g High Risk 61 to 100g 41 to 60g Very High Risk 101+g 61+g</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="134"/>
                <count group_id="O2" value="146"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="69"/>
                    <measurement group_id="O2" value="80"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Days Abstinent Per Week</title>
        <description>Timeline Follow Back daily drinking data used to calculate the % of days abstinent per week.</description>
        <time_frame>Weeks 22-25</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Sugar Pill</title>
            <description>Matching placebo, sugar pill&#xD;
Placebo: Placebo tablet, white to off-white, oval shaped tablets, taken 2 times per day</description>
          </group>
          <group group_id="O2">
            <title>Gabapentin Enacarbil</title>
            <description>600 mg Gabapentin Enacarbil (Horizant)&#xD;
gabapentin enacarbil: Horizant Extended Release Tablets, 600 mg, white to off-white, oval shaped tablets, taken 2 times per day</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Days Abstinent Per Week</title>
          <description>Timeline Follow Back daily drinking data used to calculate the % of days abstinent per week.</description>
          <units>percentage of days</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="168"/>
                <count group_id="O2" value="170"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="49" spread="3.9"/>
                    <measurement group_id="O2" value="49.3" spread="3.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Heavy Drinking Days Per Week</title>
        <description>Timeline Follow Back data used to calculate the % of heavy drinking days per week. Heavy drinking is 4+ drinks per day for females and 5+ drinks per day for males</description>
        <time_frame>Weeks 22-25</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Sugar Pill</title>
            <description>Matching placebo, sugar pill&#xD;
Placebo: Placebo tablet, white to off-white, oval shaped tablets, taken 2 times per day</description>
          </group>
          <group group_id="O2">
            <title>Gabapentin Enacarbil</title>
            <description>600 mg Gabapentin Enacarbil (Horizant)&#xD;
gabapentin enacarbil: Horizant Extended Release Tablets, 600 mg, white to off-white, oval shaped tablets, taken 2 times per day</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Heavy Drinking Days Per Week</title>
          <description>Timeline Follow Back data used to calculate the % of heavy drinking days per week. Heavy drinking is 4+ drinks per day for females and 5+ drinks per day for males</description>
          <units>percentage of days</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="168"/>
                <count group_id="O2" value="170"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="46.5" spread="4.2"/>
                    <measurement group_id="O2" value="43.1" spread="4.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Weekly Mean Number of Drinks Per Week</title>
        <description>Timeline Follow Back data used to calculate the weekly mean number of drinks per week</description>
        <time_frame>Weeks 22-25</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Sugar Pill</title>
            <description>Matching placebo, sugar pill&#xD;
Placebo: Placebo tablet, white to off-white, oval shaped tablets, taken 2 times per day</description>
          </group>
          <group group_id="O2">
            <title>Gabapentin Enacarbil</title>
            <description>600 mg Gabapentin Enacarbil (Horizant)&#xD;
gabapentin enacarbil: Horizant Extended Release Tablets, 600 mg, white to off-white, oval shaped tablets, taken 2 times per day</description>
          </group>
        </group_list>
        <measure>
          <title>Weekly Mean Number of Drinks Per Week</title>
          <description>Timeline Follow Back data used to calculate the weekly mean number of drinks per week</description>
          <units>drinks per week</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="168"/>
                <count group_id="O2" value="170"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="21.4" spread="2.4"/>
                    <measurement group_id="O2" value="23.1" spread="2.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Weekly Mean Drinks Per Drinking Day</title>
        <description>Timeline Follow Back daily drinking data used to calculate the weekly mean drinks per drinking day</description>
        <time_frame>Weeks 22-25</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Sugar Pill</title>
            <description>Matching placebo, sugar pill&#xD;
Placebo: Placebo tablet, white to off-white, oval shaped tablets, taken 2 times per day</description>
          </group>
          <group group_id="O2">
            <title>Gabapentin Enacarbil</title>
            <description>600 mg Gabapentin Enacarbil (Horizant)&#xD;
gabapentin enacarbil: Horizant Extended Release Tablets, 600 mg, white to off-white, oval shaped tablets, taken 2 times per day</description>
          </group>
        </group_list>
        <measure>
          <title>Weekly Mean Drinks Per Drinking Day</title>
          <description>Timeline Follow Back daily drinking data used to calculate the weekly mean drinks per drinking day</description>
          <units>drinks per drinking day</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="168"/>
                <count group_id="O2" value="170"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.9" spread="0.4"/>
                    <measurement group_id="O2" value="4.1" spread="0.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cigarettes Per Week Among Smokers</title>
        <description>A quantity frequency interview of three questions to assess cigarette smoking behavior and other tobacco/nicotine containing products use during the study: 1) &quot;Over the past week, on how many days did you smoke cigarettes?&quot;, 2) &quot;On the days you smoked during the past week, how many cigarettes did you smoke on average?&quot;, and 3) &quot;Have you used any other tobacco or nicotine containing products besides cigarettes in the past week (e.g., cigars, cigarellos, pipes, bidis, or smokeless tobacco such as pan, chewing tobacco, or snuff, or nicotine replacement therapies such as patch or gum)?&quot;.</description>
        <time_frame>Weeks 22-25</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Sugar Pill</title>
            <description>Matching placebo, sugar pill&#xD;
Placebo: Placebo tablet, white to off-white, oval shaped tablets, taken 2 times per day</description>
          </group>
          <group group_id="O2">
            <title>Gabapentin Enacarbil</title>
            <description>600 mg Gabapentin Enacarbil (Horizant)&#xD;
gabapentin enacarbil: Horizant Extended Release Tablets, 600 mg, white to off-white, oval shaped tablets, taken 2 times per day</description>
          </group>
        </group_list>
        <measure>
          <title>Cigarettes Per Week Among Smokers</title>
          <description>A quantity frequency interview of three questions to assess cigarette smoking behavior and other tobacco/nicotine containing products use during the study: 1) &quot;Over the past week, on how many days did you smoke cigarettes?&quot;, 2) &quot;On the days you smoked during the past week, how many cigarettes did you smoke on average?&quot;, and 3) &quot;Have you used any other tobacco or nicotine containing products besides cigarettes in the past week (e.g., cigars, cigarellos, pipes, bidis, or smokeless tobacco such as pan, chewing tobacco, or snuff, or nicotine replacement therapies such as patch or gum)?&quot;.</description>
          <units>cigarettes per week</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="168"/>
                <count group_id="O2" value="170"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="61.4" spread="8.3"/>
                    <measurement group_id="O2" value="71" spread="8.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Alcohol Craving Score [Alcohol Craving Scale - Short Form (ACQ-SR-R)]</title>
        <description>The ACQ-SR-R contains 12-items adapted from the 47-item ACQ-NOW developed by Singleton et al (1994) to assess craving for alcohol among alcohol users in the current context (right now). Each item has a 1 to 7 raw score (from strongly disagree to strongly agree). Items 3, 8, and 11 are reverse keyed. A general craving index is derived by summing all items and dividing by 12. Minimum score is 1 and maximum score is 7. Higher scores are indicative of higher craving.&#xD;
Mixed effects models as stated in Section 9.4.3 of the SAP will be generated for the total score and for the 4 subscales. Covariates for these models will be identified</description>
        <time_frame>Weeks 24 and 26</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Sugar Pill</title>
            <description>Matching placebo, sugar pill&#xD;
Placebo: Placebo tablet, white to off-white, oval shaped tablets, taken 2 times per day</description>
          </group>
          <group group_id="O2">
            <title>Gabapentin Enacarbil</title>
            <description>600 mg Gabapentin Enacarbil (Horizant)&#xD;
gabapentin enacarbil: Horizant Extended Release Tablets, 600 mg, white to off-white, oval shaped tablets, taken 2 times per day</description>
          </group>
        </group_list>
        <measure>
          <title>Alcohol Craving Score [Alcohol Craving Scale - Short Form (ACQ-SR-R)]</title>
          <description>The ACQ-SR-R contains 12-items adapted from the 47-item ACQ-NOW developed by Singleton et al (1994) to assess craving for alcohol among alcohol users in the current context (right now). Each item has a 1 to 7 raw score (from strongly disagree to strongly agree). Items 3, 8, and 11 are reverse keyed. A general craving index is derived by summing all items and dividing by 12. Minimum score is 1 and maximum score is 7. Higher scores are indicative of higher craving.&#xD;
Mixed effects models as stated in Section 9.4.3 of the SAP will be generated for the total score and for the 4 subscales. Covariates for these models will be identified</description>
          <units>scores on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="168"/>
                <count group_id="O2" value="170"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.5" spread="0.1"/>
                    <measurement group_id="O2" value="2.5" spread="0.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Alcohol Related Consequences (ImBIBe) Score</title>
        <description>ImBIBe is a 15-item questionnaire in which the subject responds on a 5-point scale (0-4) responses to questions on the consequences of alcohol use. This scale was adapted from the Drinker Inventory of Consequences questionnaire based on FDA recommendations on patient reported outcomes (Miller &amp; Tonigen-1995). The potential range is 0-60. A higher score indicates a worse outcome. The questions are added together. A question that is missing is imputed with the average value of all other questions in the questionnaire.The total score is the sum of the individual item scores.&#xD;
Mixed effects models as stated in Section 9.4.3 will be generated for the total score. Covariates for these models will be identified</description>
        <time_frame>Weeks 24 and 26</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Sugar Pill</title>
            <description>Matching placebo, sugar pill&#xD;
Placebo: Placebo tablet, white to off-white, oval shaped tablets, taken 2 times per day</description>
          </group>
          <group group_id="O2">
            <title>Gabapentin Enacarbil</title>
            <description>600 mg Gabapentin Enacarbil (Horizant)&#xD;
gabapentin enacarbil: Horizant Extended Release Tablets, 600 mg, white to off-white, oval shaped tablets, taken 2 times per day</description>
          </group>
        </group_list>
        <measure>
          <title>Alcohol Related Consequences (ImBIBe) Score</title>
          <description>ImBIBe is a 15-item questionnaire in which the subject responds on a 5-point scale (0-4) responses to questions on the consequences of alcohol use. This scale was adapted from the Drinker Inventory of Consequences questionnaire based on FDA recommendations on patient reported outcomes (Miller &amp; Tonigen-1995). The potential range is 0-60. A higher score indicates a worse outcome. The questions are added together. A question that is missing is imputed with the average value of all other questions in the questionnaire.The total score is the sum of the individual item scores.&#xD;
Mixed effects models as stated in Section 9.4.3 will be generated for the total score. Covariates for these models will be identified</description>
          <units>total score</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="168"/>
                <count group_id="O2" value="170"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.3" spread="0.7"/>
                    <measurement group_id="O2" value="9.6" spread="0.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pittsburgh Sleep Quality Index (PSQI) Score</title>
        <description>The PSQI is a 19-item questionnaire assessing the subject's overall sleep experience in the past 30 days (Buysse et al-1989). The lower the overall score, the better the person sleeps. The tool has an adequate internal reliability, validity and consistency for clinical and community samples of the various populations. Range is (0-21); &gt;6 indicative of &quot;poor&quot; sleep quality.</description>
        <time_frame>Week 26</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Sugar Pill</title>
            <description>Matching placebo, sugar pill&#xD;
Placebo: Placebo tablet, white to off-white, oval shaped tablets, taken 2 times per day</description>
          </group>
          <group group_id="O2">
            <title>Gabapentin Enacarbil</title>
            <description>600 mg Gabapentin Enacarbil (Horizant)&#xD;
gabapentin enacarbil: Horizant Extended Release Tablets, 600 mg, white to off-white, oval shaped tablets, taken 2 times per day</description>
          </group>
        </group_list>
        <measure>
          <title>Pittsburgh Sleep Quality Index (PSQI) Score</title>
          <description>The PSQI is a 19-item questionnaire assessing the subject's overall sleep experience in the past 30 days (Buysse et al-1989). The lower the overall score, the better the person sleeps. The tool has an adequate internal reliability, validity and consistency for clinical and community samples of the various populations. Range is (0-21); &gt;6 indicative of &quot;poor&quot; sleep quality.</description>
          <units>score</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="168"/>
                <count group_id="O2" value="170"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.4" spread="0.2"/>
                    <measurement group_id="O2" value="4.9" spread="0.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Beck Anxiety Inventory (BAI) Score</title>
        <description>The BAI consists of 21 questions about how the subject has been feeling in the last week, expressed as common symptoms of anxiety (such as numbness and tingling, sweating not due to heat, and fear of the worst happening). This inventory was designed to minimize the overlap with depression scales (Beck et al-1988).The BAI has a maximum score of 63. The standardized cutoffs for anxiety severity are: 0-7: minimal level of anxiety 8-15: mild anxiety 16-25: moderate anxiety 26-63: severe anxiety</description>
        <time_frame>Week 26</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Sugar Pill</title>
            <description>Matching placebo, sugar pill&#xD;
Placebo: Placebo tablet, white to off-white, oval shaped tablets, taken 2 times per day</description>
          </group>
          <group group_id="O2">
            <title>Gabapentin Enacarbil</title>
            <description>600 mg Gabapentin Enacarbil (Horizant)&#xD;
gabapentin enacarbil: Horizant Extended Release Tablets, 600 mg, white to off-white, oval shaped tablets, taken 2 times per day</description>
          </group>
        </group_list>
        <measure>
          <title>Beck Anxiety Inventory (BAI) Score</title>
          <description>The BAI consists of 21 questions about how the subject has been feeling in the last week, expressed as common symptoms of anxiety (such as numbness and tingling, sweating not due to heat, and fear of the worst happening). This inventory was designed to minimize the overlap with depression scales (Beck et al-1988).The BAI has a maximum score of 63. The standardized cutoffs for anxiety severity are: 0-7: minimal level of anxiety 8-15: mild anxiety 16-25: moderate anxiety 26-63: severe anxiety</description>
          <units>score</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="168"/>
                <count group_id="O2" value="170"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.3" spread="0.5"/>
                    <measurement group_id="O2" value="4.6" spread="0.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Beck Depression Inventory - II</title>
        <description>The BDI-II is a 21-item multiple choice questionnaire that is used for measuring the severity of depression (Beck et al-1966). Each item is scored on a scale value of 0 to 3. The standardized cutoffs for depression severity are:&#xD;
0-13: minimal depression 14-19: mild depression 20-28: moderate depression 29-63: severe depression</description>
        <time_frame>Week 26</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Sugar Pill</title>
            <description>Matching placebo, sugar pill&#xD;
Placebo: Placebo tablet, white to off-white, oval shaped tablets, taken 2 times per day</description>
          </group>
          <group group_id="O2">
            <title>Gabapentin Enacarbil</title>
            <description>600 mg Gabapentin Enacarbil (Horizant)&#xD;
gabapentin enacarbil: Horizant Extended Release Tablets, 600 mg, white to off-white, oval shaped tablets, taken 2 times per day</description>
          </group>
        </group_list>
        <measure>
          <title>Beck Depression Inventory - II</title>
          <description>The BDI-II is a 21-item multiple choice questionnaire that is used for measuring the severity of depression (Beck et al-1966). Each item is scored on a scale value of 0 to 3. The standardized cutoffs for depression severity are:&#xD;
0-13: minimal depression 14-19: mild depression 20-28: moderate depression 29-63: severe depression</description>
          <units>score</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="168"/>
                <count group_id="O2" value="170"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.2" spread="0.5"/>
                    <measurement group_id="O2" value="6.5" spread="0.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>AEs were assessed from Week 1 - Week 29.</time_frame>
      <desc>General symptoms were collected via an open ended question: &quot;How have you been feeling since your last visit or the last time we spoke?&quot;</desc>
      <group_list>
        <group group_id="E1">
          <title>Sugar Pill</title>
          <description>Matching placebo, sugar pill&#xD;
Placebo: Placebo tablet, white to off-white, oval shaped tablets, taken 2 times per day</description>
        </group>
        <group group_id="E2">
          <title>Gabapentin Enacarbil</title>
          <description>600 mg Gabapentin Enacarbil (Horizant)&#xD;
gabapentin enacarbil: Horizant Extended Release Tablets, 600 mg, white to off-white, oval shaped tablets, taken 2 times per day</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (16.1)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="170"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="170"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Bradycardia during colonoscopy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="168"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="170"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Stomach Ulcer</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="168"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="170"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>pneumonia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="168"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="170"/>
              </event>
              <event>
                <sub_title>Head Laceration complicated by orbital fracture</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="168"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="170"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Orbital Fracture</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="168"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="170"/>
              </event>
              <event>
                <sub_title>Acute Intoxication</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="168"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="170"/>
              </event>
              <event>
                <sub_title>Comminuted impacted fracture of the right humeral head</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="168"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="170"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back Pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="168"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="170"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Alcohol Withdrawal</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="168"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="170"/>
              </event>
              <event>
                <sub_title>migraine with left eye drooping</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="168"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="170"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Suicidality</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="168"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="170"/>
              </event>
              <event>
                <sub_title>Paranoia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="168"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="170"/>
              </event>
              <event>
                <sub_title>Alcohol Use Disorder</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="168"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="170"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA (16.1)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="155" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="157" subjects_at_risk="170"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="170"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="23" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="17" subjects_at_risk="170"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="15" subjects_at_risk="170"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="26" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="44" subjects_at_risk="170"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="21" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="19" subjects_at_risk="170"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="22" subjects_at_risk="170"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood Pressure diastolic increased</sub_title>
                <counts group_id="E1" subjects_affected="42" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="43" subjects_at_risk="170"/>
              </event>
              <event>
                <sub_title>Blood Pressure Systolic increase</sub_title>
                <counts group_id="E1" subjects_affected="32" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="33" subjects_at_risk="170"/>
              </event>
              <event>
                <sub_title>Aspartate Aminotransferase Increased</sub_title>
                <counts group_id="E1" subjects_affected="26" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="24" subjects_at_risk="170"/>
              </event>
              <event>
                <sub_title>Gamma-glutamyltransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="19" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="30" subjects_at_risk="170"/>
              </event>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="19" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="170"/>
              </event>
              <event>
                <sub_title>Blood creatinine increased</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="170"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="170"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back Pain</sub_title>
                <counts group_id="E1" subjects_affected="19" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="170"/>
              </event>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="170"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="47" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="38" subjects_at_risk="170"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="23" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="36" subjects_at_risk="170"/>
              </event>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="30" subjects_at_risk="170"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="18" subjects_at_risk="170"/>
              </event>
              <event>
                <sub_title>Paraesthesia</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="170"/>
              </event>
              <event>
                <sub_title>Tremor</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="170"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="170"/>
              </event>
              <event>
                <sub_title>Abnormal dreams</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="170"/>
              </event>
              <event>
                <sub_title>Agitation</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="170"/>
              </event>
              <event>
                <sub_title>Depressed mood</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="170"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="13" subjects_at_risk="170"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="170"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="170"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>Restricts disclosure until the main study paper is published.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Megan Ryan</name_or_title>
      <organization>NIAAA</organization>
      <phone>3014434225</phone>
      <email>mryan1@mail.nih.gov</email>
    </point_of_contact>
  </clinical_results>
</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/NCT02252536
org study id: NCIG - 006
nct id: NCT02252536
lead sponsor: 
collaborator: 
has dmc: Yes
The purpose of this study is to determine whether gabapentin enacarbil is effective in the
      treatment of problems with alcohol.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Percentage of Subjects With no Heavy Drinking Days (PSNHDD)
time frame: Weeks 22-25
description: The primary objective of the study is to compare the efficacy of HORIZANT (gabapentin enacarbil) Extended-Release Tablets 600 mg twice daily (BID) with matched placebo on the primary alcohol consumption outcome endpoint, percentage of subjects with no heavy drinking days (PSNHDD) during the last 4 weeks of treatment, among patients with Alcohol Use Disorder (AUD).
measure: Percentage of Subjects Abstinent From Alcohol (Key Secondary Endpoint)
time frame: Weeks 22-25
description: Timeline Follow-back drinking data is used to calculate the % of subjects that report not drinking alcohol during weeks 22-25
measure: Percentage of Subjects With a World Health Organization (WHO) Drinking Risk Category Decrease of at Least 1-level
time frame: Weeks 22-25
description: Timeline Follow Back data is used to calculate the % of participants that decrease at least 1-level WHO drinking risk category. The WHO has developed a drinking risk categorical scale that can be used in a responder analysis approach to assess clinically relevant decreases in alcohol consumption (Aubin et al-2015). The WHO 1- and 2-level decrease endpoints are the percentage of subjects experiencing at least 1- and 2-level decrease in WHO levels of alcohol consumption, respectively, from the level at baseline (the period including the 28 days before screening) to the level during the last 4 weeks of the maintenance phase (Study Weeks 22-25). The WHO levels are as follows:
Males Females Low Risk 1 to 40g 1 to 20g Medium Risk 41 to 60g 21 to 40g High Risk 61 to 100g 41 to 60g Very High Risk 101+g 61+g
measure: Percentage of Subjects With a World Health Organization (WHO) Drinking Risk Category Decrease of at Least 2-levels
time frame: Weeks 22-25
description: Timeline Follow Back data is used to calculate the % of participants that decrease at least 1-level WHO drinking risk category. The WHO has developed a drinking risk categorical scale that can be used in a responder analysis approach to assess clinically relevant decreases in alcohol consumption (Aubin et al-2015). The WHO 1- and 2-level decrease endpoints are the percentage of subjects experiencing at least 1- and 2-level decrease in WHO levels of alcohol consumption, respectively, from the level at baseline (the period including the 28 days before screening) to the level during the last 4 weeks of the maintenance phase (Study Weeks 22-25). The WHO levels are as follows:
Males Females Low Risk 1 to 40g 1 to 20g Medium Risk 41 to 60g 21 to 40g High Risk 61 to 100g 41 to 60g Very High Risk 101+g 61+g
measure: Percentage of Days Abstinent Per Week
time frame: Weeks 22-25
description: Timeline Follow Back daily drinking data used to calculate the % of days abstinent per week.
measure: Percentage of Heavy Drinking Days Per Week
time frame: Weeks 22-25
description: Timeline Follow Back data used to calculate the % of heavy drinking days per week. Heavy drinking is 4+ drinks per day for females and 5+ drinks per day for males
measure: Weekly Mean Number of Drinks Per Week
time frame: Weeks 22-25
description: Timeline Follow Back data used to calculate the weekly mean number of drinks per week
measure: Weekly Mean Drinks Per Drinking Day
time frame: Weeks 22-25
description: Timeline Follow Back daily drinking data used to calculate the weekly mean drinks per drinking day
measure: Cigarettes Per Week Among Smokers
time frame: Weeks 22-25
description: A quantity frequency interview of three questions to assess cigarette smoking behavior and other tobacco/nicotine containing products use during the study: 1) "Over the past week, on how many days did you smoke cigarettes?", 2) "On the days you smoked during the past week, how many cigarettes did you smoke on average?", and 3) "Have you used any other tobacco or nicotine containing products besides cigarettes in the past week (e.g., cigars, cigarellos, pipes, bidis, or smokeless tobacco such as pan, chewing tobacco, or snuff, or nicotine replacement therapies such as patch or gum)?".
measure: Alcohol Craving Score [Alcohol Craving Scale - Short Form (ACQ-SR-R)]
time frame: Weeks 24 and 26
description: The ACQ-SR-R contains 12-items adapted from the 47-item ACQ-NOW developed by Singleton et al (1994) to assess craving for alcohol among alcohol users in the current context (right now). Each item has a 1 to 7 raw score (from strongly disagree to strongly agree). Items 3, 8, and 11 are reverse keyed. A general craving index is derived by summing all items and dividing by 12. Minimum score is 1 and maximum score is 7. Higher scores are indicative of higher craving.
Mixed effects models as stated in Section 9.4.3 of the SAP will be generated for the total score and for the 4 subscales. Covariates for these models will be identified
measure: Alcohol Related Consequences (ImBIBe) Score
time frame: Weeks 24 and 26
description: ImBIBe is a 15-item questionnaire in which the subject responds on a 5-point scale (0-4) responses to questions on the consequences of alcohol use. This scale was adapted from the Drinker Inventory of Consequences questionnaire based on FDA recommendations on patient reported outcomes (Miller & Tonigen-1995). The potential range is 0-60. A higher score indicates a worse outcome. The questions are added together. A question that is missing is imputed with the average value of all other questions in the questionnaire.The total score is the sum of the individual item scores.
Mixed effects models as stated in Section 9.4.3 will be generated for the total score. Covariates for these models will be identified
measure: Pittsburgh Sleep Quality Index (PSQI) Score
time frame: Week 26
description: The PSQI is a 19-item questionnaire assessing the subject's overall sleep experience in the past 30 days (Buysse et al-1989). The lower the overall score, the better the person sleeps. The tool has an adequate internal reliability, validity and consistency for clinical and community samples of the various populations. Range is (0-21); >6 indicative of "poor" sleep quality.
measure: Beck Anxiety Inventory (BAI) Score
time frame: Week 26
description: The BAI consists of 21 questions about how the subject has been feeling in the last week, expressed as common symptoms of anxiety (such as numbness and tingling, sweating not due to heat, and fear of the worst happening). This inventory was designed to minimize the overlap with depression scales (Beck et al-1988).The BAI has a maximum score of 63. The standardized cutoffs for anxiety severity are: 0-7: minimal level of anxiety 8-15: mild anxiety 16-25: moderate anxiety 26-63: severe anxiety
measure: Beck Depression Inventory - II
time frame: Week 26
description: The BDI-II is a 21-item multiple choice questionnaire that is used for measuring the severity of depression (Beck et al-1966). Each item is scored on a scale value of 0 to 3. The standardized cutoffs for depression severity are:
0-13: minimal depression 14-19: mild depression 20-28: moderate depression 29-63: severe depression
arm group label: Sugar Pill
arm group type: Placebo Comparator
description: Matching placebo, sugar pill
arm group label: Gabapentin Enacarbil
arm group type: Active Comparator
description: 600 mg Gabapentin Enacarbil (Horizant)
intervention type: Drug
intervention name: gabapentin enacarbil
description: Horizant Extended Release Tablets, 600 mg, white to off-white, oval shaped tablets, taken 2 times per day
arm group label: Gabapentin Enacarbil
other name: Horizant Extended Release Tablets
intervention type: Drug
intervention name: Placebo
description: Placebo tablet, white to off-white, oval shaped tablets, taken 2 times per day
arm group label: Sugar Pill
criteria: 
gender: All
minimum age: 21 Years
maximum age: N/A
healthy volunteers: No
last name: Raye Z. Litten, Ph.D.
role: Study Chair
affiliation: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
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country: United States
responsible party type: Sponsor
mesh term: Alcoholism
mesh term: Alcohol Drinking
mesh term: Gabapentin
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