<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/NCT04502589</url>
  </required_header>
  <id_info>
    <org_study_id>HM20015846</org_study_id>
    <secondary_id>R21AA026681</secondary_id>
    <nct_id>NCT04502589</nct_id>
  </id_info>
  <brief_title>Open Label Pilot Study of Perampanel for the Treatment of Alcohol Use Disorder</brief_title>
  <official_title>Open Label Pilot Study of Perampanel for the Treatment of Alcohol Use Disorder</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Virginia Commonwealth University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute on Alcohol Abuse and Alcoholism (NIAAA)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Virginia Commonwealth University</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this research study is to test the safety, tolerability, and effectiveness of&#xD;
      the drug Perampanel when used in persons who drink and wish to stop drinking. Perampanel has&#xD;
      been approved by the U.S. Food and Drug Administration (FDA) for the treatment of seizures&#xD;
      but has not yet been approved to treat alcohol use disorders. For this reason, it is&#xD;
      considered an investigational drug. Some people in this study will receive Perampanel alone&#xD;
      and some people will receive Perampanel and Disulfiram, this will be determined by the&#xD;
      pharmacy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Participants will be asked to take a medication (Perampanel or Perampanel + Disulfiram) every&#xD;
      day for approximately 8 weeks and have weekly study visits. At these visits, participants&#xD;
      will be asked questions about their medical history, drinking behavior and life events, have&#xD;
      bloodwork checked routinely, have regular medication counseling, and perform some computer&#xD;
      tasks. Throughout the study, there will be regular phone calls from staff. Participants will&#xD;
      also be asked to use a device called &quot;Soberlink&quot; which is like an at-home breathalyzer test&#xD;
      to help track progress throughout the study.&#xD;
&#xD;
      Participants will be randomly assigned (like the flip of a coin) to receive either Perampanel&#xD;
      alone or Peramanel and Disulfiram.&#xD;
&#xD;
      Participation in this study will last up to 10 weeks. Approximately 20 individuals will&#xD;
      participate in this study.&#xD;
&#xD;
      This study will sequence all or part of participant's DNA. This is a necessary part of the&#xD;
      study.&#xD;
&#xD;
      Before starting the study, participants may be referred to an alcohol detoxification program&#xD;
      (medical treatment of an alcoholic), if clinically indicated.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 15, 2020</start_date>
  <completion_date type="Actual">August 11, 2021</completion_date>
  <primary_completion_date type="Actual">August 11, 2021</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>20 subjects with AUD will be randomized 1:1 to one of two groups; perampanel by itself, and perampanel combined with disulfiram.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percent Abstinent Days</measure>
    <time_frame>End of treatment, up to 12 weeks</time_frame>
    <description>Participant will report the number of alcoholic drinks they consumed during the previous weeks period. Participants will be accessed for the full 12 week titration plus treatment period. However, for the purposes of the study, the percent of days the participant was abstinent will be calculated and reported only for the 8 week active treatment period.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Alcohol Craving</measure>
    <time_frame>Baseline to end of treatment, up to 12 weeks</time_frame>
    <description>Alcohol craving will be assessed using the Alcohol Urge Questionnaire (AUG). The AUG is an 8-item survey asking participants to rate their craving for alcohol on a 1 to 7 scale. The answers are summed yielding a score ranging from 7 to 56 with higher scores indicated higher alcohol craving.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Heavy Drinking Days</measure>
    <time_frame>End of treatment, Up to 8 weeks</time_frame>
    <description>Participant will report the number of alcoholic drinks they consumed during the previous weeks period. Based on participant report, the percent of days the participant drank heavily will be calculated over the 8 week active treatment period.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">4</enrollment>
  <condition>Alcohol Disorders</condition>
  <arm_group>
    <arm_group_label>perampanel by itself</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Perapanel with Disulfiram</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Perampanel Tablet</intervention_name>
    <description>Subjects will be titrated over 3 weeks to a target dose of 8mg perampanel daily in both groups</description>
    <arm_group_label>Perapanel with Disulfiram</arm_group_label>
    <arm_group_label>perampanel by itself</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Disulfiram</intervention_name>
    <description>Disulfiram will be kept at 250mg daily</description>
    <arm_group_label>Perapanel with Disulfiram</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Men and women ages 21-70 with DSM-5 AUD;&#xD;
&#xD;
          2. regular heavy drinkers as defined by averaging ≥ 2 heavy drinking days per week over&#xD;
             the 60 days baseline pre-treatment TLFB, and recognize a need to completely stop&#xD;
             drinking;&#xD;
&#xD;
          3. willingness to provide written, informed consent to participate in the study;&#xD;
&#xD;
          4. Individuals with LFTs that are no more than 2-3 times above the normal levels and with&#xD;
             a Child-Pugh score of no greater than 5 will be included and&#xD;
&#xD;
          5. women of child-bearing potential (i.e., no hysterectomy, bilateral oophorectomy, or&#xD;
             tubal ligation or &lt;2 years postmenopausal), must be non-lactating, practicing a&#xD;
             reliable method of birth control, and have a negative serum pregnancy test prior to&#xD;
             initiation of treatment.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. a current, clinically significant physical disease [i.e., neurologic, renal,&#xD;
             pulmonary, cardiovascular, hepatic] on the basis of medical history, physical&#xD;
             examination, or routine laboratory evaluation that, in the context of the study would&#xD;
             represent a risk to the subject, or significant laboratory abnormalities related to&#xD;
             hepatic function such as marked elevations of hepatic aminotransferase levels (i.e.,&#xD;
             AST and ALT) or direct bilirubin;&#xD;
&#xD;
          2. history of renal compromise or current renal disease (as evidenced by serum creatinine&#xD;
             above our laboratory's reference limit of 1.7 mg/dL;&#xD;
&#xD;
          3. history of seizure disorder;&#xD;
&#xD;
          4. use of any of a number of medications that might prominently influence drinking&#xD;
             patterns or cause risk of harm or injury (e.g., other anticonvulsants, medications to&#xD;
             treat AUD, opioid pain medication), currently taking CNS depressants (e.g.&#xD;
             benzodiazepines, barbiturates, sedating antihistamines;&#xD;
&#xD;
          5. schizophrenia, bipolar disorder, current major depressive episode, or substantial&#xD;
             suicide or violence risk on the basis of history or psychiatric examination;&#xD;
&#xD;
          6. currently dependent on stimulants, opioids or sedatives;&#xD;
&#xD;
          7. subjects with any substantial alcohol withdrawal will be required to be detoxified by&#xD;
             regular clinical services prior to study entry;&#xD;
&#xD;
          8. are currently taking any medication that is a moderate to strong CYP3A4 inhibitor or&#xD;
             inducer if participants are required to initiate these medications by an outside&#xD;
             provider during the course of this study, they will be tapered off the study regimen&#xD;
             and we will have them terminate early)&#xD;
&#xD;
          9. are taking phenytoin or warfarin&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Albert Arias, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Virginia Commonwealth University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Virginia Commonwealth University Inst. for Drug and Alcohol Studies</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23219</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>August 4, 2020</study_first_submitted>
  <study_first_submitted_qc>August 4, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 6, 2020</study_first_posted>
  <results_first_submitted>August 10, 2022</results_first_submitted>
  <results_first_submitted_qc>October 5, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">October 7, 2022</results_first_posted>
  <last_update_submitted>October 5, 2022</last_update_submitted>
  <last_update_submitted_qc>October 5, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 7, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Alcoholism</mesh_term>
    <mesh_term>Alcohol-Related Disorders</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Disulfiram</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>June 30, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/89/NCT04502589/Prot_SAP_002.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>August 10, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/89/NCT04502589/ICF_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Perampanel by Itself</title>
          <description>Perampanel Tablet: Subjects will be titrated over 3 weeks to a target dose of 8mg perampanel daily in both groups</description>
        </group>
        <group group_id="P2">
          <title>Perapanel With Disulfiram</title>
          <description>Perampanel Tablet: Subjects will be titrated over 3 weeks to a target dose of 8mg perampanel daily in both groups&#xD;
Disulfiram: Disulfiram will be kept at 250mg daily</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Perampanel by Itself</title>
          <description>Perampanel Tablet: Subjects will be titrated over 3 weeks to a target dose of 8mg perampanel daily in both groups</description>
        </group>
        <group group_id="B2">
          <title>Perapanel With Disulfiram</title>
          <description>Perampanel Tablet: Subjects will be titrated over 3 weeks to a target dose of 8mg perampanel daily in both groups&#xD;
Disulfiram: Disulfiram will be kept at 250mg daily</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="2"/>
            <count group_id="B2" value="2"/>
            <count group_id="B3" value="4"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</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>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</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_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="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="4"/>
                  </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="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</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_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="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</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>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="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</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>Unknown or Not Reported</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_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percent Abstinent Days</title>
        <description>Participant will report the number of alcoholic drinks they consumed during the previous weeks period. Participants will be accessed for the full 12 week titration plus treatment period. However, for the purposes of the study, the percent of days the participant was abstinent will be calculated and reported only for the 8 week active treatment period.</description>
        <time_frame>End of treatment, up to 12 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Perampanel by Itself</title>
            <description>Perampanel Tablet: Subjects will be titrated over 3 weeks to a target dose of 8mg perampanel daily in both groups</description>
          </group>
          <group group_id="O2">
            <title>Perapanel With Disulfiram</title>
            <description>Perampanel Tablet: Subjects will be titrated over 3 weeks to a target dose of 8mg perampanel daily in both groups&#xD;
Disulfiram: Disulfiram will be kept at 250mg daily</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Abstinent Days</title>
          <description>Participant will report the number of alcoholic drinks they consumed during the previous weeks period. Participants will be accessed for the full 12 week titration plus treatment period. However, for the purposes of the study, the percent of days the participant was abstinent will be calculated and reported only for the 8 week active treatment period.</description>
          <units>Percentage of days</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
                <count group_id="O2" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.13" lower_limit="0" upper_limit="6.25"/>
                    <measurement group_id="O2" value="100" lower_limit="100" upper_limit="100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Alcohol Craving</title>
        <description>Alcohol craving will be assessed using the Alcohol Urge Questionnaire (AUG). The AUG is an 8-item survey asking participants to rate their craving for alcohol on a 1 to 7 scale. The answers are summed yielding a score ranging from 7 to 56 with higher scores indicated higher alcohol craving.</description>
        <time_frame>Baseline to end of treatment, up to 12 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Perampanel by Itself</title>
            <description>Perampanel Tablet: Subjects will be titrated over 3 weeks to a target dose of 8mg perampanel daily in both groups</description>
          </group>
          <group group_id="O2">
            <title>Perapanel With Disulfiram</title>
            <description>Perampanel Tablet: Subjects will be titrated over 3 weeks to a target dose of 8mg perampanel daily in both groups&#xD;
Disulfiram: Disulfiram will be kept at 250mg daily</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Alcohol Craving</title>
          <description>Alcohol craving will be assessed using the Alcohol Urge Questionnaire (AUG). The AUG is an 8-item survey asking participants to rate their craving for alcohol on a 1 to 7 scale. The answers are summed yielding a score ranging from 7 to 56 with higher scores indicated higher alcohol craving.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
                <count group_id="O2" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4" lower_limit="2" upper_limit="6"/>
                    <measurement group_id="O2" value="-1" lower_limit="-2" upper_limit="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Heavy Drinking Days</title>
        <description>Participant will report the number of alcoholic drinks they consumed during the previous weeks period. Based on participant report, the percent of days the participant drank heavily will be calculated over the 8 week active treatment period.</description>
        <time_frame>End of treatment, Up to 8 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Perampanel by Itself</title>
            <description>Perampanel Tablet: Subjects will be titrated over 3 weeks to a target dose of 8mg perampanel daily in both groups</description>
          </group>
          <group group_id="O2">
            <title>Perapanel With Disulfiram</title>
            <description>Perampanel Tablet: Subjects will be titrated over 3 weeks to a target dose of 8mg perampanel daily in both groups&#xD;
Disulfiram: Disulfiram will be kept at 250mg daily</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Heavy Drinking Days</title>
          <description>Participant will report the number of alcoholic drinks they consumed during the previous weeks period. Based on participant report, the percent of days the participant drank heavily will be calculated over the 8 week active treatment period.</description>
          <units>percentage of days</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
                <count group_id="O2" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="73.60" lower_limit="65.6" upper_limit="81.6"/>
                    <measurement group_id="O2" value="0" lower_limit="0" upper_limit="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>At baseline and weekly for eight weeks</time_frame>
      <desc>The Systematic Assessment for Treatment Emergent Events (SAFTEE) is a NIAAA developed assessment for adverse events in alcohol pharmacotherapy trials. The assessment was modified to assess for known side effects of perampanel.</desc>
      <group_list>
        <group group_id="E1">
          <title>Perampanel by Itself</title>
          <description>Perampanel Tablet: Subjects will be titrated over 3 weeks to a target dose of 8mg perampanel daily in both groups</description>
        </group>
        <group group_id="E2">
          <title>Perapanel With Disulfiram</title>
          <description>Perampanel Tablet: Subjects will be titrated over 3 weeks to a target dose of 8mg perampanel daily in both groups&#xD;
Disulfiram: Disulfiram will be kept at 250mg daily</description>
        </group>
      </group_list>
      <serious_events>
        <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="2"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Vehicle accident</sub_title>
                <description>Vehicle accident due to Drowsiness without injury</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <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="2" subjects_at_risk="2"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Irregular Heartbeat</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Double Vision</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dry Mouth</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="2"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Loss of Appetite</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Nausea/Vomiting</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Breathing Diffuculties</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Drowsiness</sub_title>
                <counts group_id="E1" events="5" subjects_affected="2" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="5" subjects_affected="2" subjects_at_risk="2"/>
                <counts group_id="E2" events="4" subjects_affected="2" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Lightheadedness</sub_title>
                <counts group_id="E1" events="4" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Loss of Balance</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Shortness of Breath</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Unsteady Walking</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Weakness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased Coordination</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Trouble Speaking or Swallowing</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Unusual Skin Sensations</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Aggression/Anger</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Agitation</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Confusion/Slow Thinking</sub_title>
                <counts group_id="E1" events="4" subjects_affected="2" subjects_at_risk="2"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Depressed Mood</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Hostility</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="2"/>
                <counts group_id="E2" events="4" subjects_affected="2" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Irritability</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Panic Attacks</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Restlessness</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Speech Problems</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Itching</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Albert Arias, M.D.</name_or_title>
      <organization>Virginia Commonwealth University</organization>
      <phone>(804) 828-5793</phone>
      <email>albert.arias@vcuhealth.org</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/NCT04502589
org study id: HM20015846
secondary id: R21AA026681
nct id: NCT04502589
lead sponsor: 
collaborator: 
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this research study is to test the safety, tolerability, and effectiveness of
      the drug Perampanel when used in persons who drink and wish to stop drinking. Perampanel has
      been approved by the U.S. Food and Drug Administration (FDA) for the treatment of seizures
      but has not yet been approved to treat alcohol use disorders. For this reason, it is
      considered an investigational drug. Some people in this study will receive Perampanel alone
      and some people will receive Perampanel and Disulfiram, this will be determined by the
      pharmacy.
Participants will be asked to take a medication (Perampanel or Perampanel + Disulfiram) every
      day for approximately 8 weeks and have weekly study visits. At these visits, participants
      will be asked questions about their medical history, drinking behavior and life events, have
      bloodwork checked routinely, have regular medication counseling, and perform some computer
      tasks. Throughout the study, there will be regular phone calls from staff. Participants will
      also be asked to use a device called "Soberlink" which is like an at-home breathalyzer test
      to help track progress throughout the study.

      Participants will be randomly assigned (like the flip of a coin) to receive either Perampanel
      alone or Peramanel and Disulfiram.

      Participation in this study will last up to 10 weeks. Approximately 20 individuals will
      participate in this study.

      This study will sequence all or part of participant's DNA. This is a necessary part of the
      study.

      Before starting the study, participants may be referred to an alcohol detoxification program
      (medical treatment of an alcoholic), if clinically indicated.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: 20 subjects with AUD will be randomized 1:1 to one of two groups; perampanel by itself, and perampanel combined with disulfiram.
primary purpose: Treatment
masking: None (Open Label)
measure: Percent Abstinent Days
time frame: End of treatment, up to 12 weeks
description: Participant will report the number of alcoholic drinks they consumed during the previous weeks period. Participants will be accessed for the full 12 week titration plus treatment period. However, for the purposes of the study, the percent of days the participant was abstinent will be calculated and reported only for the 8 week active treatment period.
measure: Change in Alcohol Craving
time frame: Baseline to end of treatment, up to 12 weeks
description: Alcohol craving will be assessed using the Alcohol Urge Questionnaire (AUG). The AUG is an 8-item survey asking participants to rate their craving for alcohol on a 1 to 7 scale. The answers are summed yielding a score ranging from 7 to 56 with higher scores indicated higher alcohol craving.
measure: Percent Heavy Drinking Days
time frame: End of treatment, Up to 8 weeks
description: Participant will report the number of alcoholic drinks they consumed during the previous weeks period. Based on participant report, the percent of days the participant drank heavily will be calculated over the 8 week active treatment period.
arm group label: perampanel by itself
arm group type: Active Comparator
arm group label: Perapanel with Disulfiram
arm group type: Active Comparator
intervention type: Drug
intervention name: Perampanel Tablet
description: Subjects will be titrated over 3 weeks to a target dose of 8mg perampanel daily in both groups
arm group label: Perapanel with Disulfiram
arm group label: perampanel by itself
intervention type: Drug
intervention name: Disulfiram
description: Disulfiram will be kept at 250mg daily
arm group label: Perapanel with Disulfiram
criteria: 
gender: All
minimum age: 21 Years
maximum age: 70 Years
healthy volunteers: No
last name: Albert Arias, MD, PhD
role: Principal Investigator
affiliation: Virginia Commonwealth University
facility: 
country: United States
responsible party type: Sponsor
mesh term: Alcoholism
mesh term: Alcohol-Related Disorders
mesh term: Disulfiram
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 