<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/NCT01725152</url>
  </required_header>
  <id_info>
    <org_study_id>1042-0800</org_study_id>
    <nct_id>NCT01725152</nct_id>
  </id_info>
  <brief_title>Ganaxolone Treatment in Children With Fragile X Syndrome</brief_title>
  <official_title>A Controlled, Double-blind, Crossover Trial of Ganaxolone in Children With Fragile X Syndrome</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Marinus Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of California, Davis</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>U.S. Army Medical Research and Development Command</agency>
      <agency_class>U.S. Fed</agency_class>
    </collaborator>
  </sponsors>
  <source>Marinus Pharmaceuticals</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This Phase 2 proof-of-concept study is a double-blind, randomized, placebo-controlled,&#xD;
      crossover study to investigate ganaxolone treatment in children with fragile x syndrome&#xD;
      (FXS). The objective of the study is to assess the safety, tolerability and efficacy of&#xD;
      ganaxolone in the treatment of anxiety and attention in subjects with FXS.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a single center study conducted at University of California Davis (UCD) MIND&#xD;
      Institute. Children with FXS between the ages of 6-17 years, inclusive will be randomized at&#xD;
      a 1:1 ratio to receive ganaxolone or placebo treatment for 6 weeks, discontinue treatment and&#xD;
      washout for 2 weeks, and then cross over to the opposite treatment for another 6 weeks.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2012</start_date>
  <completion_date type="Actual">November 1, 2016</completion_date>
  <primary_completion_date type="Actual">October 16, 2015</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>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Clinical Global Impression-Improvement (CGI-I) Scale</measure>
    <time_frame>Week 14 (End of Treatment)</time_frame>
    <description>The CGI-I scale is a clinician-rated 7-point scale used to assess how much the participant's illness had improved or worsened relative to a Baseline state at the beginning of the intervention. It was rated as: 1. &quot;very much improved&quot;; 2. &quot;much improved&quot;; 3. &quot;minimally improved&quot;; 4. &quot;no change&quot;; 5. &quot;minimally worse&quot;; 6. &quot;much worse&quot;; 7. &quot;very much worse&quot;. Higher scores indicated worse condition.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pediatric Anxiety Rating Scale (PARS) Total Score</measure>
    <time_frame>Week 14 (End of Treatment)</time_frame>
    <description>Pediatric Anxiety Rating Scale (PARS) is a clinician administered measure of anxiety in children and adolescents. The PARS is comprised of a 50-item symptom checklist used to determine the presence or absence of specific anxiety symptoms during the prior week and 7 severity/impairment items, each scored from 0 to 5. The score on the 7 items allows the clinician to rate symptom severity and associated impairment on a range from 0 to 35, with higher scores reflecting greater symptom severity and associated impairment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Visual Analogue Scale (VAS)</measure>
    <time_frame>Week 14 (End of Treatment)</time_frame>
    <description>A semi-structured VAS design was employed, providing two of the three behaviors to be assessed as anxiety and attention, chosen by caregiver(s) of one additional behavior from a bank of five. This bank included sociability, attention, aggression, language, and hyperactivity/impulsivity. Parents mark on a visual line measuring 10 centimeters (cm) with &quot;worst behavior&quot; at 0 cm and &quot;best behavior&quot; at 10 cm. For each behavior the caregiver is instructed to mark their impression of behavior at Baseline visit and again at each visit. The calculated distance in cm between the baseline and each visit marks thereby demonstrates whether each behavior improved, worsened, or stayed the same during the study, and by how much. Shown here is the least square mean distance and its corresponding standard error in cm from the &quot;worst behavior&quot; side, at baseline. Smaller the value, worser the behavior.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Anxiety, Depression, and Mood Scale (ADAMS)</measure>
    <time_frame>Week 14 (End of Treatment)</time_frame>
    <description>The ADAMS is a 28-item behavior-based informant instrument rated by the parent(s), legal authorized guardian(s), or consistent caregiver(s). The scale is composed of 5 factors, which addresses Manic/Hyperactive Behavior, Depressed Mood, Social Avoidance, General Anxiety, and Obsessive/Compulsive Behavior. Items are scored on a 0-3 Likert scale that combines frequency and severity ratings (where 0=behavior has not occurred or is not a problem, 3=behavior occurs a lot or is a severe problem). Each subscale score is calculated separately; the scale range for Manic/Hyperactive Behavior is 0-15; for Depressed Mood, 0-21; for Social Avoidance, 0-21; for General Anxiety, 0-21; for Obsessive Behavior, 0-9. There is an overlapped item between Manic/Hypertension Behavior and General Anxiety; hence, the subscale ranges appear to reflect scores for 29 items instead of 28 items.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Aberrant Behavior Checklist (ABC)</measure>
    <time_frame>Week 14 (End of Treatment)</time_frame>
    <description>The ABC is a 58-item parent rated from 0 (not at all a problem) to 3 (the problem is severe in degree with 6 subscales: Irritability (includes agitation, aggression, and self-injury, 15 items) with range of scores from 0-45; Social Withdrawal/Lethargy (16 items) with range of scores from 0-48; Stereotypy (7 items) with range of scores from 0-21; Hyperactivity (16 items) with range of scores from 0-48; Inappropriate Speech (4 items) with range of scores from 0-12 and Social avoidance (4 items) with range of scores from 0-12. Higher scores indicated greater severity. Social Withdrawal and Lethargy are reporting the same scale and Social Avoidance is a subscale of Social Withdrawal; hence, the subscale ranges appear to reflect scores for 62 items instead of 58 items.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Swanson, Nolan, and Pelham-IV Questionnaire (SNAP-IV)</measure>
    <time_frame>Week 14 (End of Treatment)</time_frame>
    <description>The SNAP-IV is a revision of the Swanson, Nolan, and Pelham (SNAP) Questionnaire. The SNAP-IV: ADHD Inattention Subscale (items 1-9) scores the intensity of each item during the last seven days on a 0 to 3 scale (0=not at all, 1=just a little, 2=pretty much, 3=very much). Possible scores ranged from 0-27; higher scores indicated a greater intensity. The SNAP-IV ADHD Hyperactivity/Impulsivity Subscale (items 10-18) scores the intensity of each item in the last seven days on a 0 to 3 scale (0=not at all, 1=just a little, 2=pretty much, 3=very much). Possible scores ranged from 0-27; higher scores indicated a greater intensity. SNAP-IV ADHD Combined Scale score (inattention + hyperactivity/impulsivity) ranged from 0-54. A low score of 0 indicates less inattention + hyperactivity/impulsivity. A high score of 54 indicates more inattention + hyperactivity.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">59</enrollment>
  <condition>Fragile x Syndrome</condition>
  <arm_group>
    <arm_group_label>Ganaxolone then Placebo</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants first received ganaxolone. They were first titrated up to the 12 milligram per kilogram (mg/kg) three times daily (tid) during a 2-week titration phase, then maintained on that dose for an additional 4 weeks. After a washout period of 2 weeks, participants received placebo for a duration of 6 weeks (from week 8 to 14).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo then Ganaxolone</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants first received placebo. They were first titrated up to the 12 mg/kg tid during a 2-week titration phase, then maintained on that dose for an additional 4 weeks. After a washout period of 2 weeks, participants received ganaxolone for a duration of 6 weeks (from week 8 to 14).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ganaxolone</intervention_name>
    <description>oral suspension, given in 3 divided doses</description>
    <arm_group_label>Ganaxolone then Placebo</arm_group_label>
    <arm_group_label>Placebo then Ganaxolone</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>oral suspension, given in 3 divided doses</description>
    <arm_group_label>Ganaxolone then Placebo</arm_group_label>
    <arm_group_label>Placebo then Ganaxolone</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  molecular documentation of FMR1 full mutation&#xD;
&#xD;
          -  ages 6-17 yrs, inclusive&#xD;
&#xD;
          -  sexually active subjects are required to use a medically acceptable form of birth&#xD;
             control&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  non-English or Spanish speaking subjects&#xD;
&#xD;
          -  concomitant systemic steroid, vigabatrin, felbamate and ketoconazole&#xD;
&#xD;
          -  changes in medications within last 2 months&#xD;
&#xD;
          -  clinically unstable medical disease, progressive CNS disease/disorder&#xD;
&#xD;
          -  history of recurrent status epilepticus&#xD;
&#xD;
          -  unwilling to withhold grapefruit or grapefruit juice for the duration of the study&#xD;
&#xD;
          -  actively suicidal&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Years</minimum_age>
    <maximum_age>17 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>M.I.N.D. Institute at University of California at Davis Medical Center</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95817</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Antwerp University Hospital</name>
      <address>
        <city>Edegem</city>
        <zip>2650</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>November 7, 2012</study_first_submitted>
  <study_first_submitted_qc>November 8, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 12, 2012</study_first_posted>
  <results_first_submitted>June 30, 2022</results_first_submitted>
  <results_first_submitted_qc>March 15, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">April 10, 2023</results_first_posted>
  <disposition_first_submitted>June 15, 2018</disposition_first_submitted>
  <disposition_first_submitted_qc>June 15, 2018</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">June 19, 2018</disposition_first_posted>
  <last_update_submitted>March 15, 2023</last_update_submitted>
  <last_update_submitted_qc>March 15, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 10, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>fragile x syndrome</keyword>
  <keyword>ganaxolone</keyword>
  <keyword>anxiety</keyword>
  <keyword>attention</keyword>
  <keyword>pediatric</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fragile X Syndrome</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ganaxolone</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>A total of 48 participants from the University of California at Davis Medical Center site and 11 participants from a Belgium site between November 1, 2012 and November 1, 2016 were enrolled in the study.</recruitment_details>
      <pre_assignment_details>59 participants were randomized in the study.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Ganaxolone, Then Placebo</title>
          <description>Participants received ganaxolone were first titrated up to the 12 milligram per kilogram (mg/kg) three times daily (tid) during a 2-week titration phase, then maintained on that dose for an additional 4 weeks. After a washout period of 2 weeks, they received placebo for a duration of 6 weeks (from week 8 to 14).</description>
        </group>
        <group group_id="P2">
          <title>Placebo, Then Ganaxolone</title>
          <description>Participants received placebo were first titrated up to the 12 mg/kg tid during a 2-week titration phase, then maintained on that dose for an additional 4 weeks. After a washout period of 2 weeks, they received ganaxolone for a duration of 6 weeks (from week 8 to 14).</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Treatment Period 1 (Week 1 to Week 6)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="30"/>
                <participants group_id="P2" count="29"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="26"/>
                <participants group_id="P2" count="29"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Consent Withdrawn</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>
          <title>Washout Period (2 Weeks)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="26"/>
                <participants group_id="P2" count="29"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="26"/>
                <participants group_id="P2" count="29"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Treatment Period 2 (Week 8 to Week 14)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="26"/>
                <participants group_id="P2" count="29"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="25"/>
                <participants group_id="P2" count="26"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Safety Set included all participants who have taken at least one dose of study drug in Treatment period 1.</population>
      <group_list>
        <group group_id="B1">
          <title>Ganaxolone, Then Placebo</title>
          <description>Participants received ganaxolone were first titrated up to the 12 mg/kg tid during a 2-week titration phase, then maintained on that dose for an additional 4 weeks. After a washout period of 2 weeks, they received placebo for a duration of 6 weeks (from week 8 to 14).</description>
        </group>
        <group group_id="B2">
          <title>Placebo, Then Ganaxolone</title>
          <description>Participants received placebo were first titrated up to the 12 mg/kg tid during a 2-week titration phase, then maintained on that dose for an additional 4 weeks. After a washout period of 2 weeks, they received ganaxolone for a duration of 6 weeks (from week 8 to 14).</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="30"/>
            <count group_id="B2" value="29"/>
            <count group_id="B3" value="59"/>
          </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="10.58" spread="3.245"/>
                    <measurement group_id="B2" value="11.33" spread="3.368"/>
                    <measurement group_id="B3" value="10.95" spread="3.299"/>
                  </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="3"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="27"/>
                    <measurement group_id="B2" value="23"/>
                    <measurement group_id="B3" value="50"/>
                  </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="5"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="25"/>
                    <measurement group_id="B2" value="23"/>
                    <measurement group_id="B3" value="48"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <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>
          <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="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="4"/>
                  </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="4"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="22"/>
                    <measurement group_id="B2" value="23"/>
                    <measurement group_id="B3" value="45"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <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>Clinical Global Impression-Improvement (CGI-I) Scale</title>
        <description>The CGI-I scale is a clinician-rated 7-point scale used to assess how much the participant's illness had improved or worsened relative to a Baseline state at the beginning of the intervention. It was rated as: 1. &quot;very much improved&quot;; 2. &quot;much improved&quot;; 3. &quot;minimally improved&quot;; 4. &quot;no change&quot;; 5. &quot;minimally worse&quot;; 6. &quot;much worse&quot;; 7. &quot;very much worse&quot;. Higher scores indicated worse condition.</description>
        <time_frame>Week 14 (End of Treatment)</time_frame>
        <population>Intention-to-Treat (ITT) Population consisted of all participants who received medication and who had at least one post-Baseline assessment. Only those participants with data available at the specified data points were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Ganaxolone</title>
            <description>Participants who received Ganaxolone up to 12 mg/kg tid in the first 6 weeks or last 6 weeks of the study.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants who received placebo (matching Ganaxolone) in the first 6 weeks or last 6 weeks of the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Clinical Global Impression-Improvement (CGI-I) Scale</title>
          <description>The CGI-I scale is a clinician-rated 7-point scale used to assess how much the participant's illness had improved or worsened relative to a Baseline state at the beginning of the intervention. It was rated as: 1. &quot;very much improved&quot;; 2. &quot;much improved&quot;; 3. &quot;minimally improved&quot;; 4. &quot;no change&quot;; 5. &quot;minimally worse&quot;; 6. &quot;much worse&quot;; 7. &quot;very much worse&quot;. Higher scores indicated worse condition.</description>
          <population>Intention-to-Treat (ITT) Population consisted of all participants who received medication and who had at least one post-Baseline assessment. Only those participants with data available at the specified data points were analyzed.</population>
          <units>Scores on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="52"/>
                <count group_id="O2" value="54"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.4" spread="0.13"/>
                    <measurement group_id="O2" value="3.5" spread="0.13"/>
                  </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>
            <groups_desc>Null hypothesis of no treatment difference in CGI-I will be assessed using a linear mixed-effects model for repeated measures, accounting for treatment (ganaxolone versus placebo) and period at a significant level of 0.05. A sample size of 30 participants in each arm/group was planned in the study will have 90% power to detect a modest effect size of 0.6 at level 0.05 in CGI-I. With a possible dropout rate of 15%, the power for testing the effect size becomes 84%.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.4475</p_value>
            <method>Linear mixed-effect</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pediatric Anxiety Rating Scale (PARS) Total Score</title>
        <description>Pediatric Anxiety Rating Scale (PARS) is a clinician administered measure of anxiety in children and adolescents. The PARS is comprised of a 50-item symptom checklist used to determine the presence or absence of specific anxiety symptoms during the prior week and 7 severity/impairment items, each scored from 0 to 5. The score on the 7 items allows the clinician to rate symptom severity and associated impairment on a range from 0 to 35, with higher scores reflecting greater symptom severity and associated impairment.</description>
        <time_frame>Week 14 (End of Treatment)</time_frame>
        <population>ITT Population. Only those participants with data available at the specified data points were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Ganaxolone</title>
            <description>Participants who received Ganaxolone up to 12 mg/kg tid in the first 6 weeks or last 6 weeks of the study.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants who received placebo (matching Ganaxolone) in the first 6 weeks or last 6 weeks of the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Pediatric Anxiety Rating Scale (PARS) Total Score</title>
          <description>Pediatric Anxiety Rating Scale (PARS) is a clinician administered measure of anxiety in children and adolescents. The PARS is comprised of a 50-item symptom checklist used to determine the presence or absence of specific anxiety symptoms during the prior week and 7 severity/impairment items, each scored from 0 to 5. The score on the 7 items allows the clinician to rate symptom severity and associated impairment on a range from 0 to 35, with higher scores reflecting greater symptom severity and associated impairment.</description>
          <population>ITT Population. Only those participants with data available at the specified data points were analyzed.</population>
          <units>Scores on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="52"/>
                <count group_id="O2" value="54"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.3" spread="0.54"/>
                    <measurement group_id="O2" value="9.2" spread="0.54"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Visual Analogue Scale (VAS)</title>
        <description>A semi-structured VAS design was employed, providing two of the three behaviors to be assessed as anxiety and attention, chosen by caregiver(s) of one additional behavior from a bank of five. This bank included sociability, attention, aggression, language, and hyperactivity/impulsivity. Parents mark on a visual line measuring 10 centimeters (cm) with &quot;worst behavior&quot; at 0 cm and &quot;best behavior&quot; at 10 cm. For each behavior the caregiver is instructed to mark their impression of behavior at Baseline visit and again at each visit. The calculated distance in cm between the baseline and each visit marks thereby demonstrates whether each behavior improved, worsened, or stayed the same during the study, and by how much. Shown here is the least square mean distance and its corresponding standard error in cm from the &quot;worst behavior&quot; side, at baseline. Smaller the value, worser the behavior.</description>
        <time_frame>Week 14 (End of Treatment)</time_frame>
        <population>ITT Population. Only those participants with data available at the specified data points were analyzed</population>
        <group_list>
          <group group_id="O1">
            <title>Ganaxolone</title>
            <description>Participants who received Ganaxolone up to 12 mg/kg tid in the first 6 weeks or last 6 weeks of the study.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants who received placebo (matching Ganaxolone) in the first 6 weeks or last 6 weeks of the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Visual Analogue Scale (VAS)</title>
          <description>A semi-structured VAS design was employed, providing two of the three behaviors to be assessed as anxiety and attention, chosen by caregiver(s) of one additional behavior from a bank of five. This bank included sociability, attention, aggression, language, and hyperactivity/impulsivity. Parents mark on a visual line measuring 10 centimeters (cm) with &quot;worst behavior&quot; at 0 cm and &quot;best behavior&quot; at 10 cm. For each behavior the caregiver is instructed to mark their impression of behavior at Baseline visit and again at each visit. The calculated distance in cm between the baseline and each visit marks thereby demonstrates whether each behavior improved, worsened, or stayed the same during the study, and by how much. Shown here is the least square mean distance and its corresponding standard error in cm from the &quot;worst behavior&quot; side, at baseline. Smaller the value, worser the behavior.</description>
          <population>ITT Population. Only those participants with data available at the specified data points were analyzed</population>
          <units>Centimeters (cm)</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="51"/>
                <count group_id="O2" value="54"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Severity of Anxiety</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.6" spread="0.27"/>
                    <measurement group_id="O2" value="5.0" spread="0.26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Severity of Attention</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.4" spread="0.24"/>
                    <measurement group_id="O2" value="3.9" spread="0.24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Severity of Target Behavior 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.4" spread="0.28"/>
                    <measurement group_id="O2" value="3.9" spread="0.27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Anxiety, Depression, and Mood Scale (ADAMS)</title>
        <description>The ADAMS is a 28-item behavior-based informant instrument rated by the parent(s), legal authorized guardian(s), or consistent caregiver(s). The scale is composed of 5 factors, which addresses Manic/Hyperactive Behavior, Depressed Mood, Social Avoidance, General Anxiety, and Obsessive/Compulsive Behavior. Items are scored on a 0-3 Likert scale that combines frequency and severity ratings (where 0=behavior has not occurred or is not a problem, 3=behavior occurs a lot or is a severe problem). Each subscale score is calculated separately; the scale range for Manic/Hyperactive Behavior is 0-15; for Depressed Mood, 0-21; for Social Avoidance, 0-21; for General Anxiety, 0-21; for Obsessive Behavior, 0-9. There is an overlapped item between Manic/Hypertension Behavior and General Anxiety; hence, the subscale ranges appear to reflect scores for 29 items instead of 28 items.</description>
        <time_frame>Week 14 (End of Treatment)</time_frame>
        <population>ITT Population. Only those participants with data available at the specified data points were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Ganaxolone</title>
            <description>Participants who received Ganaxolone up to 12 mg/kg tid in the first 6 weeks or last 6 weeks of the study.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants who received placebo (matching Ganaxolone) in the first 6 weeks or last 6 weeks of the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Anxiety, Depression, and Mood Scale (ADAMS)</title>
          <description>The ADAMS is a 28-item behavior-based informant instrument rated by the parent(s), legal authorized guardian(s), or consistent caregiver(s). The scale is composed of 5 factors, which addresses Manic/Hyperactive Behavior, Depressed Mood, Social Avoidance, General Anxiety, and Obsessive/Compulsive Behavior. Items are scored on a 0-3 Likert scale that combines frequency and severity ratings (where 0=behavior has not occurred or is not a problem, 3=behavior occurs a lot or is a severe problem). Each subscale score is calculated separately; the scale range for Manic/Hyperactive Behavior is 0-15; for Depressed Mood, 0-21; for Social Avoidance, 0-21; for General Anxiety, 0-21; for Obsessive Behavior, 0-9. There is an overlapped item between Manic/Hypertension Behavior and General Anxiety; hence, the subscale ranges appear to reflect scores for 29 items instead of 28 items.</description>
          <population>ITT Population. Only those participants with data available at the specified data points were analyzed.</population>
          <units>Scores on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="50"/>
                <count group_id="O2" value="54"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Manic/Hyperactive Behavior Total</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="50"/>
                    <count group_id="O2" value="54"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.4" spread="0.42"/>
                    <measurement group_id="O2" value="7.8" spread="0.40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Depress Mood Total</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="49"/>
                    <count group_id="O2" value="54"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.5" spread="0.32"/>
                    <measurement group_id="O2" value="2.6" spread="0.32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Social Avoidance Total</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="50"/>
                    <count group_id="O2" value="54"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.8" spread="0.42"/>
                    <measurement group_id="O2" value="6.3" spread="0.41"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>General Anxiety Total</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="50"/>
                    <count group_id="O2" value="53"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.2" spread="0.45"/>
                    <measurement group_id="O2" value="7.0" spread="0.44"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Obsessive/Compulsive Behavior Total</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="50"/>
                    <count group_id="O2" value="54"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.7" spread="0.21"/>
                    <measurement group_id="O2" value="2.8" spread="0.20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Aberrant Behavior Checklist (ABC)</title>
        <description>The ABC is a 58-item parent rated from 0 (not at all a problem) to 3 (the problem is severe in degree with 6 subscales: Irritability (includes agitation, aggression, and self-injury, 15 items) with range of scores from 0-45; Social Withdrawal/Lethargy (16 items) with range of scores from 0-48; Stereotypy (7 items) with range of scores from 0-21; Hyperactivity (16 items) with range of scores from 0-48; Inappropriate Speech (4 items) with range of scores from 0-12 and Social avoidance (4 items) with range of scores from 0-12. Higher scores indicated greater severity. Social Withdrawal and Lethargy are reporting the same scale and Social Avoidance is a subscale of Social Withdrawal; hence, the subscale ranges appear to reflect scores for 62 items instead of 58 items.</description>
        <time_frame>Week 14 (End of Treatment)</time_frame>
        <population>ITT Population. Only those participants with data available at the specified data points were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Ganaxolone</title>
            <description>Participants who received Ganaxolone up to 12 mg/kg tid in the first 6 weeks or last 6 weeks of the study.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants who received placebo (matching Ganaxolone) in the first 6 weeks or last 6 weeks of the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Aberrant Behavior Checklist (ABC)</title>
          <description>The ABC is a 58-item parent rated from 0 (not at all a problem) to 3 (the problem is severe in degree with 6 subscales: Irritability (includes agitation, aggression, and self-injury, 15 items) with range of scores from 0-45; Social Withdrawal/Lethargy (16 items) with range of scores from 0-48; Stereotypy (7 items) with range of scores from 0-21; Hyperactivity (16 items) with range of scores from 0-48; Inappropriate Speech (4 items) with range of scores from 0-12 and Social avoidance (4 items) with range of scores from 0-12. Higher scores indicated greater severity. Social Withdrawal and Lethargy are reporting the same scale and Social Avoidance is a subscale of Social Withdrawal; hence, the subscale ranges appear to reflect scores for 62 items instead of 58 items.</description>
          <population>ITT Population. Only those participants with data available at the specified data points were analyzed.</population>
          <units>Scores on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="50"/>
                <count group_id="O2" value="54"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Total - Subscale I (Irritability)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="49"/>
                    <count group_id="O2" value="53"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15.7" spread="0.87"/>
                    <measurement group_id="O2" value="16.1" spread="0.86"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Total - Subscale II (Social Withdrawal/Lethargy)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="50"/>
                    <count group_id="O2" value="53"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.6" spread="0.53"/>
                    <measurement group_id="O2" value="5.7" spread="0.54"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Total - Subscale III - (Stereotypy)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="50"/>
                    <count group_id="O2" value="54"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.7" spread="0.40"/>
                    <measurement group_id="O2" value="6.4" spread="0.39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Total - Subscale IV (Hyperactivity)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="50"/>
                    <count group_id="O2" value="54"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.3" spread="0.65"/>
                    <measurement group_id="O2" value="12.3" spread="0.62"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Total - Subscale V (Inappropriate Speech)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="50"/>
                    <count group_id="O2" value="54"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.1" spread="0.32"/>
                    <measurement group_id="O2" value="5.3" spread="0.31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Total - Subscale VI (Social Avoidance)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="50"/>
                    <count group_id="O2" value="54"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.4" spread="0.22"/>
                    <measurement group_id="O2" value="2.8" spread="0.21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Swanson, Nolan, and Pelham-IV Questionnaire (SNAP-IV)</title>
        <description>The SNAP-IV is a revision of the Swanson, Nolan, and Pelham (SNAP) Questionnaire. The SNAP-IV: ADHD Inattention Subscale (items 1-9) scores the intensity of each item during the last seven days on a 0 to 3 scale (0=not at all, 1=just a little, 2=pretty much, 3=very much). Possible scores ranged from 0-27; higher scores indicated a greater intensity. The SNAP-IV ADHD Hyperactivity/Impulsivity Subscale (items 10-18) scores the intensity of each item in the last seven days on a 0 to 3 scale (0=not at all, 1=just a little, 2=pretty much, 3=very much). Possible scores ranged from 0-27; higher scores indicated a greater intensity. SNAP-IV ADHD Combined Scale score (inattention + hyperactivity/impulsivity) ranged from 0-54. A low score of 0 indicates less inattention + hyperactivity/impulsivity. A high score of 54 indicates more inattention + hyperactivity.</description>
        <time_frame>Week 14 (End of Treatment)</time_frame>
        <population>ITT Population. Only those participants with data available at the specified data points were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Ganaxolone</title>
            <description>Participants who received Ganaxolone up to 12 mg/kg tid in the first 6 weeks or last 6 weeks of the study.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants who received placebo (matching Ganaxolone) in the first 6 weeks or last 6 weeks of the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Swanson, Nolan, and Pelham-IV Questionnaire (SNAP-IV)</title>
          <description>The SNAP-IV is a revision of the Swanson, Nolan, and Pelham (SNAP) Questionnaire. The SNAP-IV: ADHD Inattention Subscale (items 1-9) scores the intensity of each item during the last seven days on a 0 to 3 scale (0=not at all, 1=just a little, 2=pretty much, 3=very much). Possible scores ranged from 0-27; higher scores indicated a greater intensity. The SNAP-IV ADHD Hyperactivity/Impulsivity Subscale (items 10-18) scores the intensity of each item in the last seven days on a 0 to 3 scale (0=not at all, 1=just a little, 2=pretty much, 3=very much). Possible scores ranged from 0-27; higher scores indicated a greater intensity. SNAP-IV ADHD Combined Scale score (inattention + hyperactivity/impulsivity) ranged from 0-54. A low score of 0 indicates less inattention + hyperactivity/impulsivity. A high score of 54 indicates more inattention + hyperactivity.</description>
          <population>ITT Population. Only those participants with data available at the specified data points were analyzed.</population>
          <units>Scores on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="50"/>
                <count group_id="O2" value="53"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>ADHD Inattention</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15.5" spread="0.66"/>
                    <measurement group_id="O2" value="14.6" spread="0.62"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ADHD Hyperactivity/Impulsive</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13.9" spread="0.66"/>
                    <measurement group_id="O2" value="12.6" spread="0.64"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ADHD Combined</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29.3" spread="1.19"/>
                    <measurement group_id="O2" value="27.1" spread="1.14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Up to 14 Weeks</time_frame>
      <desc>Safety Population included all participants who received at least one dose of intervention. One participant mistakenly did not cross over to receive placebo and remained on Ganaxolone during Period 2 as a result of a pharmacy error.</desc>
      <group_list>
        <group group_id="E1">
          <title>Ganaxolone</title>
          <description>Participants who received Ganaxolone up to 12 mg/kg tid in the first 6 weeks or last 6 weeks of the study.</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Participants who received placebo (matching Ganaxolone) in the first 6 weeks or last 6 weeks of the study.</description>
        </group>
      </group_list>
      <serious_events>
        <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="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="54"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA 16.0</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="49" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="46" subjects_at_risk="54"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Cerumen impaction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Tympanic membrane disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="54"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Blepharitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="54"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Abdominal discomfort</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Abdominal pain lower</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Faecal incontinence</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Salivary hypersecretion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="54"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="29" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Condition aggravated</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Irritability</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Thirst</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Hyperpyrexia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="54"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Seasonal allergy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="54"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Rhinitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Otitis media</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Candida nappy rash</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Ear infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Otitis externa</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Pharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="54"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Arthropod bite</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Scratch</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Burns first degree</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Excoriation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Ligament sprain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Lip injury</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Sunburn</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Thermal burn</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Tooth avulsion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Wound</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="54"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Transaminases increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="54"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Increased appetite</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Hypoglycaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="54"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" subjects_affected="20" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Hypersomnia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Coordination abnormal</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Poor quality sleep</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Psychomotor hyperactivity</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Repetitive speech</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Balance disorder</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Drooling</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Dysarthria</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Lethargy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Petit mal epilepsy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Speech disorder</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Tremor</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="54"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Agitation</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Aggression</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Emotional disorder</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Self injurious behaviour</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Stereotypy</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Abnormal behaviour</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Sleep disorder</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Terminal insomnia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Tic</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Affect lability</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Binge eating</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Dysphemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Negativism</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Nervousness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Obsessive thoughts</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Sleep talking</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Staring</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="54"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Urinary incontinence</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Incontinence</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Ketonuria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="54"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Dysmenorrhoea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Nipple swelling</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="54"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Rhinorrhoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Respiratory tract congestion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract congestion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="54"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Acne</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Dermal cyst</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Dermatitis diaper</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Eczema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Night sweats</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="54"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Social circumstances</title>
            <event_list>
              <event>
                <sub_title>Treatment noncompliance</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="54"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Dental operation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="54"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Aortic dilatation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Hot flush</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Pallor</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="54"/>
              </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>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>Marinus</name_or_title>
      <organization>Marinus Pharmaceuticals, Inc.</organization>
      <phone>484-801-4670</phone>
      <email>clinicaltrials@marinuspharma.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/NCT01725152
org study id: 1042-0800
nct id: NCT01725152
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
This Phase 2 proof-of-concept study is a double-blind, randomized, placebo-controlled,
      crossover study to investigate ganaxolone treatment in children with fragile x syndrome
      (FXS). The objective of the study is to assess the safety, tolerability and efficacy of
      ganaxolone in the treatment of anxiety and attention in subjects with FXS.
This is a single center study conducted at University of California Davis (UCD) MIND
      Institute. Children with FXS between the ages of 6-17 years, inclusive will be randomized at
      a 1:1 ratio to receive ganaxolone or placebo treatment for 6 weeks, discontinue treatment and
      washout for 2 weeks, and then cross over to the opposite treatment for another 6 weeks.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Clinical Global Impression-Improvement (CGI-I) Scale
time frame: Week 14 (End of Treatment)
description: The CGI-I scale is a clinician-rated 7-point scale used to assess how much the participant's illness had improved or worsened relative to a Baseline state at the beginning of the intervention. It was rated as: 1. "very much improved"; 2. "much improved"; 3. "minimally improved"; 4. "no change"; 5. "minimally worse"; 6. "much worse"; 7. "very much worse". Higher scores indicated worse condition.
measure: Pediatric Anxiety Rating Scale (PARS) Total Score
time frame: Week 14 (End of Treatment)
description: Pediatric Anxiety Rating Scale (PARS) is a clinician administered measure of anxiety in children and adolescents. The PARS is comprised of a 50-item symptom checklist used to determine the presence or absence of specific anxiety symptoms during the prior week and 7 severity/impairment items, each scored from 0 to 5. The score on the 7 items allows the clinician to rate symptom severity and associated impairment on a range from 0 to 35, with higher scores reflecting greater symptom severity and associated impairment.
measure: Visual Analogue Scale (VAS)
time frame: Week 14 (End of Treatment)
description: A semi-structured VAS design was employed, providing two of the three behaviors to be assessed as anxiety and attention, chosen by caregiver(s) of one additional behavior from a bank of five. This bank included sociability, attention, aggression, language, and hyperactivity/impulsivity. Parents mark on a visual line measuring 10 centimeters (cm) with "worst behavior" at 0 cm and "best behavior" at 10 cm. For each behavior the caregiver is instructed to mark their impression of behavior at Baseline visit and again at each visit. The calculated distance in cm between the baseline and each visit marks thereby demonstrates whether each behavior improved, worsened, or stayed the same during the study, and by how much. Shown here is the least square mean distance and its corresponding standard error in cm from the "worst behavior" side, at baseline. Smaller the value, worser the behavior.
measure: Anxiety, Depression, and Mood Scale (ADAMS)
time frame: Week 14 (End of Treatment)
description: The ADAMS is a 28-item behavior-based informant instrument rated by the parent(s), legal authorized guardian(s), or consistent caregiver(s). The scale is composed of 5 factors, which addresses Manic/Hyperactive Behavior, Depressed Mood, Social Avoidance, General Anxiety, and Obsessive/Compulsive Behavior. Items are scored on a 0-3 Likert scale that combines frequency and severity ratings (where 0=behavior has not occurred or is not a problem, 3=behavior occurs a lot or is a severe problem). Each subscale score is calculated separately; the scale range for Manic/Hyperactive Behavior is 0-15; for Depressed Mood, 0-21; for Social Avoidance, 0-21; for General Anxiety, 0-21; for Obsessive Behavior, 0-9. There is an overlapped item between Manic/Hypertension Behavior and General Anxiety; hence, the subscale ranges appear to reflect scores for 29 items instead of 28 items.
measure: Aberrant Behavior Checklist (ABC)
time frame: Week 14 (End of Treatment)
description: The ABC is a 58-item parent rated from 0 (not at all a problem) to 3 (the problem is severe in degree with 6 subscales: Irritability (includes agitation, aggression, and self-injury, 15 items) with range of scores from 0-45; Social Withdrawal/Lethargy (16 items) with range of scores from 0-48; Stereotypy (7 items) with range of scores from 0-21; Hyperactivity (16 items) with range of scores from 0-48; Inappropriate Speech (4 items) with range of scores from 0-12 and Social avoidance (4 items) with range of scores from 0-12. Higher scores indicated greater severity. Social Withdrawal and Lethargy are reporting the same scale and Social Avoidance is a subscale of Social Withdrawal; hence, the subscale ranges appear to reflect scores for 62 items instead of 58 items.
measure: Swanson, Nolan, and Pelham-IV Questionnaire (SNAP-IV)
time frame: Week 14 (End of Treatment)
description: The SNAP-IV is a revision of the Swanson, Nolan, and Pelham (SNAP) Questionnaire. The SNAP-IV: ADHD Inattention Subscale (items 1-9) scores the intensity of each item during the last seven days on a 0 to 3 scale (0=not at all, 1=just a little, 2=pretty much, 3=very much). Possible scores ranged from 0-27; higher scores indicated a greater intensity. The SNAP-IV ADHD Hyperactivity/Impulsivity Subscale (items 10-18) scores the intensity of each item in the last seven days on a 0 to 3 scale (0=not at all, 1=just a little, 2=pretty much, 3=very much). Possible scores ranged from 0-27; higher scores indicated a greater intensity. SNAP-IV ADHD Combined Scale score (inattention + hyperactivity/impulsivity) ranged from 0-54. A low score of 0 indicates less inattention + hyperactivity/impulsivity. A high score of 54 indicates more inattention + hyperactivity.
arm group label: Ganaxolone then Placebo
arm group type: Experimental
description: Participants first received ganaxolone. They were first titrated up to the 12 milligram per kilogram (mg/kg) three times daily (tid) during a 2-week titration phase, then maintained on that dose for an additional 4 weeks. After a washout period of 2 weeks, participants received placebo for a duration of 6 weeks (from week 8 to 14).
arm group label: Placebo then Ganaxolone
arm group type: Experimental
description: Participants first received placebo. They were first titrated up to the 12 mg/kg tid during a 2-week titration phase, then maintained on that dose for an additional 4 weeks. After a washout period of 2 weeks, participants received ganaxolone for a duration of 6 weeks (from week 8 to 14).
intervention type: Drug
intervention name: Ganaxolone
description: oral suspension, given in 3 divided doses
arm group label: Ganaxolone then Placebo
arm group label: Placebo then Ganaxolone
intervention type: Drug
intervention name: Placebo
description: oral suspension, given in 3 divided doses
arm group label: Ganaxolone then Placebo
arm group label: Placebo then Ganaxolone
criteria: 
gender: All
minimum age: 6 Years
maximum age: 17 Years
healthy volunteers: No
facility: 
facility: 
country: Belgium
country: United States
responsible party type: Sponsor
mesh term: Fragile X Syndrome
mesh term: Syndrome
mesh term: Ganaxolone
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 