<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/NCT03242928</url>
  </required_header>
  <id_info>
    <org_study_id>CAFQ056X2201</org_study_id>
    <secondary_id>2017-000736-33</secondary_id>
    <nct_id>NCT03242928</nct_id>
  </id_info>
  <brief_title>Study to Investigate Whether AFQ056 Reduces Cocaine Use in Patients Diagnosed With Cocaine Use Disorder (CUD)</brief_title>
  <official_title>A Randomized, Subject and Investigator Blinded, Placebo-controlled, Parallel Group Study to Investigate Whether AFQ056 Reduces Cocaine Use in Patients Diagnosed With Cocaine Use Disorder (CUD)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Novartis Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Novartis</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study assessed whether AFQ056 had a beneficial effect by reducing cocaine use in Cocaine&#xD;
      Use Disorder (CUD) patients as assessed by Timeline Follow-Back cocaine self-report.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This was a randomized, subject- and Investigator-blinded, parallel-group, placebo-controlled&#xD;
      study in subjects with CUD. The study consisted of a 17-day screening period followed by a&#xD;
      12-day baseline, a 98-day outpatient treatment period (14-day up-titration dose regimen&#xD;
      followed by 84-day maintenance dose), and an End of Study evaluation visit approximately 14&#xD;
      days after the last study drug administration. The total duration for each subject in the&#xD;
      study was approximately 20 weeks including screening and baseline.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 4, 2017</start_date>
  <completion_date type="Actual">December 16, 2019</completion_date>
  <primary_completion_date type="Actual">December 16, 2019</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>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Proportion of Cocaine Use Days</measure>
    <time_frame>Day 1 up to day 98</time_frame>
    <description>The cocaine consumption was recorded once daily (Yes/No) by the subject using the Timeline Follow-Back (TLFB) cocaine assessment tool during the treatment period. For each patient, the proportion of cocaine use days was calculated by dividing the number of days of cocaine use during the treatment period, i.e. 98 days for completers and number of days between Day 1 and day of last dose in case of premature discontinuation of study treatment.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Proportion of Positive Urine Measurements of Benzoylecgonine (BE)</measure>
    <time_frame>Day 1 up to day 98</time_frame>
    <description>Urine samples were analyzed for the presence of cocaine's metabolite benzoylecgonine (BE) which is the main metabolite of cocaine present in urine. Two urine samples were provided per week to provide a quantitative measure.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of Days of Alcohol Consumption</measure>
    <time_frame>Day 1 up to day 98</time_frame>
    <description>Alcohol consumption was recorded by the subjects using the Timeline Follow-Back (TLFB) alcohol self report. The number of standard drinks were recorded daily. The proportion of days of alcohol consumption during the study treatment period was was compared using an ANCOVA model with treatment as factor and past alcohol consumption as covariate. The past consumption of alcohol was the proportion of alcohol over the 28 days preceding the screening visit, which was assessed retrospectively using the TLFB.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AFQ056 Plasma Concentrations</measure>
    <time_frame>Day 15 (0h, 2h), Day 29 (0, 2h), Day 57 (0h, 2h), Day 98 (0h,2h)</time_frame>
    <description>Plasma samples were collected to assess pharmacokinetics (PK)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">68</enrollment>
  <condition>Cocaine-related Disorder</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Matching tablet of placebo taken orally BID</description>
  </arm_group>
  <arm_group>
    <arm_group_label>AFQ056</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Mavoglurant was up titrated on a bid regimen followed by fixed-dose bid regimen: 50 mg bid from Day 1 to Day 7, 100 mg bid from Day 8 to Day 14, and then fixed-dose 200 mg bid for 84 days</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>AFQ056</intervention_name>
    <description>50 mg and 100 mg tablets taken orally</description>
    <arm_group_label>AFQ056</arm_group_label>
    <other_name>mavoglurant</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Matching placebo tablets taken orally BID</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Understand the study procedures and provide written informed consent before any&#xD;
             assessment is performed.&#xD;
&#xD;
          -  Subjects diagnosed with Cocaine Use Disorder according to DSM 5 (Diagnostic and&#xD;
             Statistical Manual of Mental Disorders, 5th Ed.).&#xD;
&#xD;
          -  Must use cocaine through snorting (intranasally) as primary route of administration.&#xD;
&#xD;
          -  Recent cocaine use confirmed by positive urine screen for 1 or more benzoylecgonine&#xD;
             (BE).&#xD;
&#xD;
          -  Must be seeking treatment for cocaine dependence and have a desire to reduce or cease&#xD;
             cocaine use.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Has current diagnosis of Substance Use Disorder (according to the DSM 5) on alcohol,&#xD;
             cannabis or other stimulants, except cocaine.&#xD;
&#xD;
          -  Meets current or lifetime DSM 5 criteria for schizophrenia or any psychotic disorder,&#xD;
             or organic mental disorder.&#xD;
&#xD;
          -  Have current treatment for Substance Use Disorder (e.g.: disulfiram, acamprosate,&#xD;
             methyl phenidate, modafinil, topiramate, immediate release dexamfetamine,or baclofen).&#xD;
&#xD;
          -  Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a&#xD;
             female after conception and until the termination of gestation, confirmed by a&#xD;
             positive hCG laboratory test&#xD;
&#xD;
          -  Have a history of any illness, condition, and use of medications that in the opinion&#xD;
             of the investigator or designee might confound the results of the study or pose&#xD;
             additional risk in administering the investigational agents to the subject or preclude&#xD;
             successful completion of the study&#xD;
&#xD;
          -  Current or/and previous treatment with concomitant medications that are strong or&#xD;
             moderate inducers/inhibitors of CYP3A4 (e.g., clarithromycin, ketoconazole, ritonavir,&#xD;
             etc.)&#xD;
&#xD;
          -  History of immunodeficiency diseases, including a positive HIV (ELISA and Western&#xD;
             blot) test result.&#xD;
&#xD;
          -  Chronic infection with Hepatitis B (HBV) or Hepatitis C (HCV).&#xD;
&#xD;
          -  Score &quot;yes&quot; on item 4 or item 5 of the Suicidal Ideation section of the CSSRS, if this&#xD;
             ideation occurred in the past 6 months, or &quot;yes&quot; on any item of the Suicidal Behavior&#xD;
             section, except for the &quot;Non-Suicidal Self-Injurious Behavior&quot; (item also included in&#xD;
             the Suicidal Behavior section), if this behavior occurred in the past 2 years.&#xD;
&#xD;
          -  Controlled hypertension&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Buenos Aires</city>
        <zip>1058</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Buenos Aires</city>
        <zip>4634</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Buenos Aires</city>
        <zip>C1405B0A</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>San Juan de Alicante</city>
        <state>Alicante</state>
        <zip>03550</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Barcelona</city>
        <state>Catalunya</state>
        <zip>08003</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Barcelona</city>
        <zip>08036</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Basel</city>
        <zip>4025</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Zuerich</city>
        <zip>8001</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Argentina</country>
    <country>Spain</country>
    <country>Switzerland</country>
  </location_countries>
  <link>
    <url>https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=689</url>
    <description>A Plain Language Trial Summary is available on novartisclinicaltrials.com</description>
  </link>
  <verification_date>October 2021</verification_date>
  <study_first_submitted>August 4, 2017</study_first_submitted>
  <study_first_submitted_qc>August 4, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 8, 2017</study_first_posted>
  <results_first_submitted>December 16, 2020</results_first_submitted>
  <results_first_submitted_qc>February 3, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">February 4, 2021</results_first_posted>
  <last_update_submitted>October 7, 2021</last_update_submitted>
  <last_update_submitted_qc>October 7, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">October 8, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Cocaine Use Disorder; cocaine dependence,AFQ056,adult, cocaine use,CUD, drug abuse, drug addiction,</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cocaine-Related Disorders</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to to respect the privacy of patients who have participated in the trail in line with applicable laws and regulations.&#xD;
This trial data availability is according to the criteria and process described on www.clinicalsutdydatarequest.com.</ipd_description>
  </patient_data>
  <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>November 15, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/28/NCT03242928/Prot_001.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>April 7, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/28/NCT03242928/SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>There were 68 patients who received study treatment.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>AFQ056</title>
          <description>Mavoglurant was up titrated on a bid regimen followed by fixed-dose bid regimen: 50 mg bid from Day 1 to Day 7, 100 mg bid from Day 8 to Day 14, and then fixed-dose 200 mg bid for 84 days</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Matching tablet of placebo taken orally BID</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="31"/>
                <participants group_id="P2" count="37"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="22"/>
                <participants group_id="P2" count="32"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</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>AFQ056</title>
          <description>Mavoglurant was up titrated on a bid regimen followed by fixed-dose bid regimen: 50 mg bid from Day 1 to Day 7, 100 mg bid from Day 8 to Day 14, and then fixed-dose 200 mg bid for 84 days</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Matching tablet of placebo taken orally BID</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="31"/>
            <count group_id="B2" value="37"/>
            <count group_id="B3" value="68"/>
          </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="35.4" spread="8.31"/>
                    <measurement group_id="B2" value="35.5" spread="9.19"/>
                    <measurement group_id="B3" value="35.4" spread="8.74"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age, Customized</title>
          <units>Participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>18 - 65 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="31"/>
                    <measurement group_id="B2" value="37"/>
                    <measurement group_id="B3" value="68"/>
                  </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="5"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="26"/>
                    <measurement group_id="B2" value="30"/>
                    <measurement group_id="B3" value="56"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>White</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="31"/>
                    <measurement group_id="B2" value="36"/>
                    <measurement group_id="B3" value="67"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Asian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Proportion of Cocaine Use Days</title>
        <description>The cocaine consumption was recorded once daily (Yes/No) by the subject using the Timeline Follow-Back (TLFB) cocaine assessment tool during the treatment period. For each patient, the proportion of cocaine use days was calculated by dividing the number of days of cocaine use during the treatment period, i.e. 98 days for completers and number of days between Day 1 and day of last dose in case of premature discontinuation of study treatment.</description>
        <time_frame>Day 1 up to day 98</time_frame>
        <population>Pharmacodynamic analysis set (PD): subjects with any available efficacy (PD) data, who received study drug for at least 14 days with no relevant protocol deviation</population>
        <group_list>
          <group group_id="O1">
            <title>AFQ056</title>
            <description>Mavoglurant was up titrated on a bid regimen followed by fixed-dose bid regimen: 50 mg bid from Day 1 to Day 7, 100 mg bid from Day 8 to Day 14, and then fixed-dose 200 mg bid for 84 days</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Matching tablet of placebo taken orally BID</description>
          </group>
        </group_list>
        <measure>
          <title>Proportion of Cocaine Use Days</title>
          <description>The cocaine consumption was recorded once daily (Yes/No) by the subject using the Timeline Follow-Back (TLFB) cocaine assessment tool during the treatment period. For each patient, the proportion of cocaine use days was calculated by dividing the number of days of cocaine use during the treatment period, i.e. 98 days for completers and number of days between Day 1 and day of last dose in case of premature discontinuation of study treatment.</description>
          <population>Pharmacodynamic analysis set (PD): subjects with any available efficacy (PD) data, who received study drug for at least 14 days with no relevant protocol deviation</population>
          <units>cocaine use days</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
                <count group_id="O2" value="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.122" spread="0.027"/>
                    <measurement group_id="O2" value="0.209" spread="0.024"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>= 0.021</p_value>
            <method>ANCOVA</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-0.087</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.037</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.161</ci_lower_limit>
            <ci_upper_limit>-0.013</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Proportion of Positive Urine Measurements of Benzoylecgonine (BE)</title>
        <description>Urine samples were analyzed for the presence of cocaine's metabolite benzoylecgonine (BE) which is the main metabolite of cocaine present in urine. Two urine samples were provided per week to provide a quantitative measure.</description>
        <time_frame>Day 1 up to day 98</time_frame>
        <group_list>
          <group group_id="O1">
            <title>AFQ056</title>
            <description>Mavoglurant was up titrated on a bid regimen followed by fixed-dose bid regimen: 50 mg bid from Day 1 to Day 7, 100 mg bid from Day 8 to Day 14, and then fixed-dose 200 mg bid for 84 days</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Matching tablet of placebo taken orally BID</description>
          </group>
        </group_list>
        <measure>
          <title>Proportion of Positive Urine Measurements of Benzoylecgonine (BE)</title>
          <description>Urine samples were analyzed for the presence of cocaine's metabolite benzoylecgonine (BE) which is the main metabolite of cocaine present in urine. Two urine samples were provided per week to provide a quantitative measure.</description>
          <units>positive urine samples</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
                <count group_id="O2" value="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.666" spread="0.057"/>
                    <measurement group_id="O2" value="0.843" spread="0.051"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>= 0.025</p_value>
            <method>ANOVA</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-0.177</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.077</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.331</ci_lower_limit>
            <ci_upper_limit>-0.023</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Proportion of Days of Alcohol Consumption</title>
        <description>Alcohol consumption was recorded by the subjects using the Timeline Follow-Back (TLFB) alcohol self report. The number of standard drinks were recorded daily. The proportion of days of alcohol consumption during the study treatment period was was compared using an ANCOVA model with treatment as factor and past alcohol consumption as covariate. The past consumption of alcohol was the proportion of alcohol over the 28 days preceding the screening visit, which was assessed retrospectively using the TLFB.</description>
        <time_frame>Day 1 up to day 98</time_frame>
        <population>Pharmacodynamic analysis set (PD): subjects with any available efficacy (PD) data, who received study drug for at least 14 days with no relevant protocol deviation</population>
        <group_list>
          <group group_id="O1">
            <title>AFQ056</title>
            <description>Mavoglurant was up titrated on a bid regimen followed by fixed-dose bid regimen: 50 mg bid from Day 1 to Day 7, 100 mg bid from Day 8 to Day 14, and then fixed-dose 200 mg bid for 84 days</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Matching tablet of placebo taken orally BID</description>
          </group>
        </group_list>
        <measure>
          <title>Proportion of Days of Alcohol Consumption</title>
          <description>Alcohol consumption was recorded by the subjects using the Timeline Follow-Back (TLFB) alcohol self report. The number of standard drinks were recorded daily. The proportion of days of alcohol consumption during the study treatment period was was compared using an ANCOVA model with treatment as factor and past alcohol consumption as covariate. The past consumption of alcohol was the proportion of alcohol over the 28 days preceding the screening visit, which was assessed retrospectively using the TLFB.</description>
          <population>Pharmacodynamic analysis set (PD): subjects with any available efficacy (PD) data, who received study drug for at least 14 days with no relevant protocol deviation</population>
          <units>alcohol consumption days</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
                <count group_id="O2" value="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.233" spread="0.030"/>
                    <measurement group_id="O2" value="0.303" spread="0.026"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>= 0.072</p_value>
            <method>ANCOVA</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-0.070</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.038</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.146</ci_lower_limit>
            <ci_upper_limit>0.006</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>AFQ056 Plasma Concentrations</title>
        <description>Plasma samples were collected to assess pharmacokinetics (PK)</description>
        <time_frame>Day 15 (0h, 2h), Day 29 (0, 2h), Day 57 (0h, 2h), Day 98 (0h,2h)</time_frame>
        <population>Number of samples available for analysis varied across time points</population>
        <group_list>
          <group group_id="O1">
            <title>AFQ056</title>
            <description>Mavoglurant was up titrated on a bid regimen followed by fixed-dose bid regimen: 50 mg bid from Day 1 to Day 7, 100 mg bid from Day 8 to Day 14, and then fixed-dose 200 mg bid for 84 days</description>
          </group>
        </group_list>
        <measure>
          <title>AFQ056 Plasma Concentrations</title>
          <description>Plasma samples were collected to assess pharmacokinetics (PK)</description>
          <population>Number of samples available for analysis varied across time points</population>
          <units>ng/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 15 0 hour</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="41.2" spread="47.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 15 2 hour</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="78.0" spread="91.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 29 0 hour</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="26"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="83.5" spread="116"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 29 2 hour</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="24"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="148" spread="131"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 57 0 hour</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="108" spread="153"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 57 2 hour</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="141" spread="153"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 98 0 hour</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="89.8" spread="148"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 98 2 hour</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="116" spread="86.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were reported from first dose of study treatment until end of study treatment plus 14 days post treatment, up to maximum duration of approximately 16 weeks</time_frame>
      <group_list>
        <group group_id="E1">
          <title>AFQ056</title>
          <description>Mavoglurant was up titrated on a bid regimen followed by fixed-dose bid regimen: 50 mg bid from Day 1 to Day 7, 100 mg bid from Day 8 to Day 14, and then fixed-dose 200 mg bid for 84 days</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Matching tablet of placebo taken orally BID</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 22.1</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="31"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Agitation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA 22.1</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="26" subjects_at_risk="31"/>
                <counts group_id="E2" subjects_affected="30" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Iron deficiency anaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Monocytosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Tachycardia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Ear pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Tinnitus</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Blepharospasm</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Diplopia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Photophobia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Photopsia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="31"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Vision blurred</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal discomfort</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" events="6" subjects_affected="3" subjects_at_risk="31"/>
                <counts group_id="E2" events="12" subjects_affected="7" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="31"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="31"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" events="4" subjects_affected="2" subjects_at_risk="31"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="31"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Gingival bleeding</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="8" subjects_affected="6" subjects_at_risk="31"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Odynophagia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Paraesthesia oral</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Regurgitation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Toothache</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E2" events="6" subjects_affected="6" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="6" subjects_affected="3" subjects_at_risk="31"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Discomfort</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="4" subjects_affected="2" subjects_at_risk="31"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Influenza like illness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" events="4" subjects_affected="2" subjects_at_risk="31"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Physical deconditioning</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Thirst</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Vessel puncture site pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Seasonal allergy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Hordeolum</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" events="7" subjects_affected="4" subjects_at_risk="31"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Laryngitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="31"/>
                <counts group_id="E2" events="10" subjects_affected="8" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Pharyngitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Pulpitis dental</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Rhinitis</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="31"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Limb injury</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Road traffic accident</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Skin abrasion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Skin laceration</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Toxicity to various agents</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="31"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Amylase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Blood creatine phosphokinase increased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="31"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Blood creatinine abnormal</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Blood creatinine increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Blood triglycerides increased</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="31"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Gamma-glutamyltransferase increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Lymphocyte count increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Neutrophil count increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Platelet count increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Red blood cell count increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>White blood cell count increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="37"/>
              </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="4" subjects_affected="4" subjects_at_risk="31"/>
                <counts group_id="E2" events="6" subjects_affected="5" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Muscle tightness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Muscle twitching</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Neck pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Rhabdomyolysis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Lipoma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="17" subjects_affected="7" subjects_at_risk="31"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="13" subjects_affected="6" subjects_at_risk="31"/>
                <counts group_id="E2" events="24" subjects_affected="10" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Muscle contractions involuntary</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Paraesthesia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="31"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Psychomotor hyperactivity</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Resting tremor</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="31"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="31"/>
                <counts group_id="E2" events="5" subjects_affected="4" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Aversion</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Depressed mood</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Depressive symptom</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Disorientation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Euphoric mood</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Feeling guilty</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Hallucination</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Hallucination, auditory</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Hallucination, olfactory</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Hallucination, visual</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="31"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Ideas of reference</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Illusion</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="31"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Initial insomnia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="9" subjects_affected="5" subjects_at_risk="31"/>
                <counts group_id="E2" events="11" subjects_affected="2" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Irritability</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Nightmare</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="31"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Paranoia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Sleep disorder</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="31"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Stress</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Nocturia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Renal pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Dysmenorrhoea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Pelvic pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Bronchospasm</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Nasal mucosal ulcer</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Rhinitis allergic</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Acne</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Hyperhidrosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" events="7" subjects_affected="2" subjects_at_risk="31"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Haematoma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Peripheral coldness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Vasospasm</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="37"/>
              </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>The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Clinical Disclosure Office</name_or_title>
      <organization>Novartis Pharma AG</organization>
      <phone>613241111</phone>
      <email>Novartis.email@Novartis.com</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/NCT03242928
org study id: CAFQ056X2201
secondary id: 2017-000736-33
nct id: NCT03242928
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study assessed whether AFQ056 had a beneficial effect by reducing cocaine use in Cocaine
      Use Disorder (CUD) patients as assessed by Timeline Follow-Back cocaine self-report.
This was a randomized, subject- and Investigator-blinded, parallel-group, placebo-controlled
      study in subjects with CUD. The study consisted of a 17-day screening period followed by a
      12-day baseline, a 98-day outpatient treatment period (14-day up-titration dose regimen
      followed by 84-day maintenance dose), and an End of Study evaluation visit approximately 14
      days after the last study drug administration. The total duration for each subject in the
      study was approximately 20 weeks including screening and baseline.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Proportion of Cocaine Use Days
time frame: Day 1 up to day 98
description: The cocaine consumption was recorded once daily (Yes/No) by the subject using the Timeline Follow-Back (TLFB) cocaine assessment tool during the treatment period. For each patient, the proportion of cocaine use days was calculated by dividing the number of days of cocaine use during the treatment period, i.e. 98 days for completers and number of days between Day 1 and day of last dose in case of premature discontinuation of study treatment.
measure: Proportion of Positive Urine Measurements of Benzoylecgonine (BE)
time frame: Day 1 up to day 98
description: Urine samples were analyzed for the presence of cocaine's metabolite benzoylecgonine (BE) which is the main metabolite of cocaine present in urine. Two urine samples were provided per week to provide a quantitative measure.
measure: Proportion of Days of Alcohol Consumption
time frame: Day 1 up to day 98
description: Alcohol consumption was recorded by the subjects using the Timeline Follow-Back (TLFB) alcohol self report. The number of standard drinks were recorded daily. The proportion of days of alcohol consumption during the study treatment period was was compared using an ANCOVA model with treatment as factor and past alcohol consumption as covariate. The past consumption of alcohol was the proportion of alcohol over the 28 days preceding the screening visit, which was assessed retrospectively using the TLFB.
measure: AFQ056 Plasma Concentrations
time frame: Day 15 (0h, 2h), Day 29 (0, 2h), Day 57 (0h, 2h), Day 98 (0h,2h)
description: Plasma samples were collected to assess pharmacokinetics (PK)
arm group label: Placebo
arm group type: Placebo Comparator
description: Matching tablet of placebo taken orally BID
arm group label: AFQ056
arm group type: Experimental
description: Mavoglurant was up titrated on a bid regimen followed by fixed-dose bid regimen: 50 mg bid from Day 1 to Day 7, 100 mg bid from Day 8 to Day 14, and then fixed-dose 200 mg bid for 84 days
intervention type: Drug
intervention name: AFQ056
description: 50 mg and 100 mg tablets taken orally
arm group label: AFQ056
other name: mavoglurant
intervention type: Drug
intervention name: Placebo
description: Matching placebo tablets taken orally BID
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Argentina
country: Spain
country: Switzerland
url: https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=689
description: A Plain Language Trial Summary is available on novartisclinicaltrials.com
responsible party type: Sponsor
mesh term: Cocaine-Related Disorders
sharing ipd: Undecided
ipd description: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to to respect the privacy of patients who have participated in the trail in line with applicable laws and regulations.
This trial data availability is according to the criteria and process described on www.clinicalsutdydatarequest.com.
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 