<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/NCT02224703</url>
  </required_header>
  <id_info>
    <org_study_id>GWEP1424</org_study_id>
    <secondary_id>2014-002939-34</secondary_id>
    <nct_id>NCT02224703</nct_id>
  </id_info>
  <brief_title>GWPCARE2 A Study to Investigate the Efficacy and Safety of Cannabidiol (GWP42003-P) in Children and Young Adults With Dravet Syndrome</brief_title>
  <official_title>A Randomized, Double-blind, Placebo-controlled Study to Investigate the Efficacy and Safety of Cannabidiol (GWP42003-P) in Children and Young Adults With Dravet Syndrome.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Jazz Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Jazz Pharmaceuticals</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      To investigate the potential antiepileptic effects of cannabidiol (GWP42003-P) in children&#xD;
      and young adults with Dravet syndrome.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study was a 2:2:1:1 randomized, double-blind, 14-week comparison of two dose levels of&#xD;
      GWP42003-P (10 milligram/kilogram [mg/kg]/day and 20 mg/kg/day) versus placebo (10 mg/kg/day&#xD;
      dose-volume equivalent and 20 mg/kg/day dose-volume equivalent; presented as pooled placebo&#xD;
      in the study). A 28-day screening period prior to randomization (to establish baseline&#xD;
      parameters) preceded the treatment period, which consisted of a 2-week titration period&#xD;
      followed by a 12-week maintenance period. The study aimed to determine the efficacy, safety,&#xD;
      and tolerability of GWP42003-P compared with placebo. 20 mg/kg/day was recommended by the&#xD;
      Data Safety Monitoring Committee (DSMC) after assessment of safety and pharmacokinetic data&#xD;
      from Part A of study GWEP1332 (NCT02091206). The first participant did not enroll into this&#xD;
      study until the DSMC reviewed the safety data from Part A of study GWEP1332 (NCT02091206).&#xD;
&#xD;
      Following study completion, all participants were invited to continue to receive GWP42003-P&#xD;
      in a separate open-label extension study (GWEP1415; NCT02224573).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 13, 2015</start_date>
  <completion_date type="Actual">April 9, 2018</completion_date>
  <primary_completion_date type="Actual">April 9, 2018</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change In Convulsive Seizures During The Treatment Period Compared To Baseline</measure>
    <time_frame>Baseline to Day 99 or Early Termination (ET)</time_frame>
    <description>Convulsive seizures were defined as tonic-clonic, tonic, clonic, or atonic. Participants or their caregivers recorded the number and type of convulsive seizures each day from screening until completion of dosing using an interactive voice response system (IVRS) diary. The primary endpoint was analyzed using negative binomial regression on the sum of the convulsive seizure counts during the treatment period, based on the ITT analysis set. Baseline included all available data prior to Day 1. Data reported as the ratio of geometric least squares mean in convulsive seizures and expressed as a percentage reduction.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change In Total Seizures During The Treatment Period Compared To Baseline</measure>
    <time_frame>Baseline to Day 99 or ET</time_frame>
    <description>Total seizures were defined as the combination of convulsive and non-convulsive seizures. Convulsive seizures were defined as tonic-clonic, tonic, clonic, or atonic seizures. Non-convulsive seizures were defined as myoclonic, countable partial, other partial, or absence seizures. Participants or their caregivers recorded the number and type of convulsive seizures and non-convulsive seizures each day from screening until completion of dosing using an IVRS diary. Change compared to baseline was calculated as per the primary outcome measure. Data reported as the ratio of geometric least squares mean in total seizures and expressed as a percentage reduction.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Participants With A ≥50% Reduction From Baseline In Convulsive Seizure Frequency During The Treatment Period</measure>
    <time_frame>Baseline to Day 99 or ET</time_frame>
    <description>Convulsive seizures were defined as tonic-clonic, tonic, clonic, or atonic. Participants or their caregivers recorded the number and type of convulsive seizures each day from screening until completion of dosing using an IVRS diary. Baseline included all available data prior to Day 1 (28-day average). Percentage change from baseline was calculated as: ([frequency during the treatment period - frequency during baseline]/frequency during baseline) x 100. The frequency during each period was based on 28-day averages and calculated as: (number of seizures in the period/number of reported days in the IVRS period) x 28. Baseline included all available data prior to Day 1 (28-day average).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Caregiver Global Impression Of Change (CGIC) At The Last Visit</measure>
    <time_frame>Baseline to Last Visit</time_frame>
    <description>On Day 1 (prior to receiving study drug), the caregiver was asked to write a brief description of the participant's overall condition as a memory aid for the CGIC questionnaire at subsequent visits. The CGIC questionnaire comprised the following question, to be rated on a 7-point scale: Since your child started treatment, please assess the status of your child's overall condition (comparing their condition now to their condition before treatment) using the scale below. The markers were: &quot;Very Much Improved&quot;; &quot;Much Improved&quot;; &quot;Slightly Improved&quot;; &quot;No Change&quot;; &quot;Slightly Worse&quot;; &quot;Much Worse&quot;; &quot;Very Much Worse&quot;. The CGIC response/score, recorded at each visit, was summarized, on both a categorical and continuous scale, by treatment group. The scores at the last scheduled visit (not including the end of taper or safety follow-up visits) at which participant's last evaluation was performed were analyzed using ordinal logistic regression.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">199</enrollment>
  <condition>Epilepsy</condition>
  <condition>Dravet Syndrome</condition>
  <arm_group>
    <arm_group_label>10 mg/kg/day GWP42003-P</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>GWP42003-P oral solution (100 mg/milliliter [mL] cannabidiol in sesame oil with anhydrous ethanol with added sweetener [sucralose] and strawberry flavoring). The 10 mg/kg/day dose was defined as 50% of the 20 mg/kg/day dose.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>20 mg/kg/day GWP42003-P</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>GWP42003-P oral solution (100 mg/mL cannabidiol in sesame oil with anhydrous ethanol with added sweetener [sucralose] and strawberry flavoring). The 20 mg/kg/day dose was recommended by the DSMC after assessment of safety and pharmacokinetic data from Part A of study GWEP1332 (NCT02091206).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo Control</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Excipients only. Participants were pooled from 2 placebo cohorts, half receiving 10 mg/kg/day dose-volume equivalent and half receiving 20 mg/kg/day dose-volume equivalent.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>GWP42003-P</intervention_name>
    <arm_group_label>10 mg/kg/day GWP42003-P</arm_group_label>
    <arm_group_label>20 mg/kg/day GWP42003-P</arm_group_label>
    <other_name>Cannabidiol</other_name>
    <other_name>CBD</other_name>
    <other_name>Epidiolex</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo Control</intervention_name>
    <arm_group_label>Placebo Control</arm_group_label>
    <other_name>Placebo</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria:&#xD;
&#xD;
          -  Participant must have been male or female, aged between 2 and 18 years (inclusive).&#xD;
&#xD;
          -  Participant must have had a documented history of Dravet syndrome that was not&#xD;
             completely controlled by current antiepileptic drugs.&#xD;
&#xD;
          -  Participant must have been taking 1 or more antiepileptic drugs at a dose that had&#xD;
             been stable for at least 4 weeks.&#xD;
&#xD;
          -  All medications or interventions for epilepsy (including ketogenic diet and vagus&#xD;
             nerve stimulation) must have been stable for 4 weeks prior to screening and&#xD;
             participant was willing to maintain a stable regimen throughout the study.&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
          -  Participant had clinically significant unstable medical conditions other than&#xD;
             epilepsy.&#xD;
&#xD;
          -  Participant had clinically relevant symptoms or a clinically significant illness in&#xD;
             the 4 weeks prior to screening or randomization, other than epilepsy.&#xD;
&#xD;
          -  Participant was currently using or had in the past used recreational cannabis,&#xD;
             medicinal cannabis, or synthetic cannabinoid-based medications (including Sativex®)&#xD;
             within the 3 months prior to study entry and was unwilling to abstain for the duration&#xD;
             for the study.&#xD;
&#xD;
          -  Participant had any known or suspected hypersensitivity to cannabinoids or any of the&#xD;
             excipients of the investigational medicinal products.&#xD;
&#xD;
          -  There were plans for the participant to travel outside their country of residence&#xD;
             during the study.&#xD;
&#xD;
          -  Any history of suicidal behavior or any suicidal ideation of type four or five on the&#xD;
             Columbia-Suicide Severity Rating Scale (Children's) at screening.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>2 Years</minimum_age>
    <maximum_age>18 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35233</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Little Rock</city>
        <state>Arkansas</state>
        <zip>72202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90027</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95816</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Hartford</city>
        <state>Connecticut</state>
        <zip>06106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33155</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Savannah</city>
        <state>Georgia</state>
        <zip>31404</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Lexington</city>
        <state>Kentucky</state>
        <zip>40536-0284</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Saint Paul</city>
        <state>Minnesota</state>
        <zip>55102</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63141</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Omaha</city>
        <state>Nebraska</state>
        <zip>68106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Lebanon</city>
        <state>New Hampshire</state>
        <zip>03756</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Buffalo</city>
        <state>New York</state>
        <zip>14203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Chapel Hill</city>
        <state>North Carolina</state>
        <zip>27599</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104-4399</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29425</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <zip>78723</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Fort Worth</city>
        <state>Texas</state>
        <zip>76104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23298-0211</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Heidelberg</city>
        <zip>3084</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Randwick</city>
        <zip>NSW 2031</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Ramat Gan</city>
        <zip>52621</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Heeze</city>
        <zip>5591 VE</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Zwolle</city>
        <zip>8025 BV</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Kraków</city>
        <zip>30-363</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Warszawa</city>
        <zip>04-730</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Łódź</city>
        <zip>93-271</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Barcelona</city>
        <zip>08022</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Madrid</city>
        <zip>28009</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Madrid</city>
        <zip>28034</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Madrid</city>
        <zip>28222</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Pamplona</city>
        <zip>31008</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Sevilla</city>
        <zip>41013</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Valencia</city>
        <zip>46026</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Israel</country>
    <country>Netherlands</country>
    <country>Poland</country>
    <country>Spain</country>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>August 21, 2014</study_first_submitted>
  <study_first_submitted_qc>August 22, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 25, 2014</study_first_posted>
  <results_first_submitted>July 11, 2019</results_first_submitted>
  <results_first_submitted_qc>July 11, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">August 1, 2019</results_first_posted>
  <last_update_submitted>September 22, 2022</last_update_submitted>
  <last_update_submitted_qc>September 22, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 28, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Cannabidiol</keyword>
  <keyword>CBD</keyword>
  <keyword>GWP42003-P</keyword>
  <keyword>Epidiolex</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Epilepsies, Myoclonic</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cannabidiol</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>September 6, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/03/NCT02224703/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>October 5, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/03/NCT02224703/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>A total of 43 sites screened participants and 38 sites (23 in the United States, 7 in Spain, 3 in Poland, 2 in Australia, 1 in Israel, and 2 in the Netherlands) randomized participants into the trial. Two sites selected (1 in Israel and 1 in the United States) did not screen any participants.</recruitment_details>
      <pre_assignment_details>To assess eligibility, participants, 2-18 years of age with Dravet syndrome had to be taking 1 or more antiepileptic drugs at a dose which had been stable; and medicated for epilepsy for at least 4 weeks were screened. A total of 285 participants were screened, of which 199 were randomized.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>10 mg/kg/Day GWP42003-P</title>
          <description>GWP42003-P oral solution (100 milligrams/milliliter [mg/mL] cannabidiol in sesame oil with anhydrous ethanol with added sweetener [sucralose] and strawberry flavoring). The 10 mg/kilogram (kg)/day dose was defined as 50% of the 20 mg/kg/day dose.</description>
        </group>
        <group group_id="P2">
          <title>20 mg/kg/Day GWP42003-P</title>
          <description>GWP42003-P oral solution (100 mg/mL cannabidiol in sesame oil with anhydrous ethanol with added sweetener [sucralose] and strawberry flavoring).The 20 mg/kg/day dose was recommended by the Data Safety Monitoring Committee (DSMC) after assessment of safety and pharmacokinetic data from Part A of study GWEP1332 (NCT02091206).</description>
        </group>
        <group group_id="P3">
          <title>Placebo Control</title>
          <description>Excipients only. Participants were pooled from 2 placebo cohorts, half receiving 10 mg/kg/day dose-volume equivalent and half receiving 20 mg/kg/day dose-volume equivalent.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="67"/>
                <participants group_id="P2" count="67"/>
                <participants group_id="P3" count="65"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Received at Least 1 Dose of Study Drug</title>
              <participants_list>
                <participants group_id="P1" count="66"/>
                <participants group_id="P2" count="67"/>
                <participants group_id="P3" count="65"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Safety Analysis Set</title>
              <participants_list>
                <participants group_id="P1" count="64">Two participants assigned to the 10 mg/kg/day dose were included in the 20 mg/kg/day group</participants>
                <participants group_id="P2" count="69">Two participants assigned to the 10 mg/kg/day dose were included in the 20 mg/kg/day group</participants>
                <participants group_id="P3" count="65"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Intent to Treat (ITT) Analysis Set</title>
              <participants_list>
                <participants group_id="P1" count="66"/>
                <participants group_id="P2" count="67"/>
                <participants group_id="P3" count="65"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="64"/>
                <participants group_id="P2" count="61"/>
                <participants group_id="P3" count="65"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" 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="0"/>
                <participants group_id="P2" count="5"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawn by investigator</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Advised by medical monitor</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawn by parent/guardian</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>10 mg/kg/Day GWP42003-P</title>
          <description>GWP42003-P oral solution (100 mg/mL cannabidiol in sesame oil with anhydrous ethanol with added sweetener [sucralose] and strawberry flavoring). The 10 mg/kg/day dose was defined as 50% of the 10 mg/kg/day dose.</description>
        </group>
        <group group_id="B2">
          <title>20 mg/kg/Day GWP42003-P</title>
          <description>GWP42003-P oral solution (100 mg/mL cannabidiol in sesame oil with anhydrous ethanol with added sweetener [sucralose] and strawberry flavoring). The 20 mg/kg/day dose was recommended by the DSMC after assessment of safety and pharmacokinetic data from Part A of study GWEP1332 (NCT02091206).</description>
        </group>
        <group group_id="B3">
          <title>Placebo Control</title>
          <description>Excipients only. Participants were pooled from 2 placebo cohorts, half receiving 10 mg/kg/day dose-volume equivalent and half receiving 20 mg/kg/day dose-volume equivalent.</description>
        </group>
        <group group_id="B4">
          <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="64"/>
            <count group_id="B2" value="69"/>
            <count group_id="B3" value="65"/>
            <count group_id="B4" value="198"/>
          </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="9.169" spread="4.1744"/>
                    <measurement group_id="B2" value="9.245" spread="4.3792"/>
                    <measurement group_id="B3" value="9.617" spread="4.5757"/>
                    <measurement group_id="B4" value="9.343" spread="4.3626"/>
                  </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="38"/>
                    <measurement group_id="B2" value="32"/>
                    <measurement group_id="B3" value="34"/>
                    <measurement group_id="B4" value="104"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="26"/>
                    <measurement group_id="B2" value="37"/>
                    <measurement group_id="B3" value="31"/>
                    <measurement group_id="B4" value="94"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>American Indian or Alaska Native</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Asian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Black or African American</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>White</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="55"/>
                    <measurement group_id="B2" value="66"/>
                    <measurement group_id="B3" value="55"/>
                    <measurement group_id="B4" value="176"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Other</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Australia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Israel</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Netherlands</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="9"/>
                    <measurement group_id="B4" value="25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Poland</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Spain</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="13"/>
                    <measurement group_id="B4" value="39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="29"/>
                    <measurement group_id="B2" value="32"/>
                    <measurement group_id="B3" value="32"/>
                    <measurement group_id="B4" value="93"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change In Convulsive Seizures During The Treatment Period Compared To Baseline</title>
        <description>Convulsive seizures were defined as tonic-clonic, tonic, clonic, or atonic. Participants or their caregivers recorded the number and type of convulsive seizures each day from screening until completion of dosing using an interactive voice response system (IVRS) diary. The primary endpoint was analyzed using negative binomial regression on the sum of the convulsive seizure counts during the treatment period, based on the ITT analysis set. Baseline included all available data prior to Day 1. Data reported as the ratio of geometric least squares mean in convulsive seizures and expressed as a percentage reduction.</description>
        <time_frame>Baseline to Day 99 or Early Termination (ET)</time_frame>
        <population>Intention-to-treat (ITT) analysis set: All participants who were randomized and dosed in the trial and had post-baseline efficacy data.</population>
        <group_list>
          <group group_id="O1">
            <title>10 mg/kg/Day GWP42003-P</title>
            <description>GWP42003-P oral solution (100 mg/mL cannabidiol in sesame oil with anhydrous ethanol with added sweetener [sucralose] and strawberry flavoring). The 10 mg/kg/day dose was defined as 50% of the 20 mg/kg/day dose.</description>
          </group>
          <group group_id="O2">
            <title>20 mg/kg/Day GWP42003-P</title>
            <description>GWP42003-P oral solution (100 mg/mL cannabidiol in sesame oil with anhydrous ethanol with added sweetener [sucralose] and strawberry flavoring). The 20 mg/kg/day dose was recommended by the DSMC after assessment of safety and pharmacokinetic data from Part A of study GWEP1332 (NCT02091206).</description>
          </group>
          <group group_id="O3">
            <title>Placebo Control</title>
            <description>Excipients only. Participants were pooled from 2 placebo cohorts, half receiving 10 mg/kg/day dose-volume equivalent and half receiving 20 mg/kg/day dose-volume equivalent.</description>
          </group>
        </group_list>
        <measure>
          <title>Change In Convulsive Seizures During The Treatment Period Compared To Baseline</title>
          <description>Convulsive seizures were defined as tonic-clonic, tonic, clonic, or atonic. Participants or their caregivers recorded the number and type of convulsive seizures each day from screening until completion of dosing using an interactive voice response system (IVRS) diary. The primary endpoint was analyzed using negative binomial regression on the sum of the convulsive seizure counts during the treatment period, based on the ITT analysis set. Baseline included all available data prior to Day 1. Data reported as the ratio of geometric least squares mean in convulsive seizures and expressed as a percentage reduction.</description>
          <population>Intention-to-treat (ITT) analysis set: All participants who were randomized and dosed in the trial and had post-baseline efficacy data.</population>
          <units>percentage reduction</units>
          <param>Geometric Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="66"/>
                <count group_id="O2" value="67"/>
                <count group_id="O3" value="65"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="48.7" lower_limit="37.9" upper_limit="57.6"/>
                    <measurement group_id="O2" value="45.7" lower_limit="34.2" upper_limit="55.2"/>
                    <measurement group_id="O3" value="26.9" lower_limit="11.9" upper_limit="39.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Model includes total number of seizures as a response variable and age group, time (baseline and treatment period), treatment, and treatment by time interaction as fixed effects, and participant as a random effect. Log-transformed number of days in which seizures were reported by period is included as an offset. Null hypothesis was that the ratio of GWP42003-P to placebo would be 1.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0299</p_value>
            <method>Negative binomial regression</method>
            <param_type>Treatment Ratio</param_type>
            <param_value>0.743</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.568</ci_lower_limit>
            <ci_upper_limit>0.971</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Model includes total number of seizures as a response variable and age group, time (baseline and treatment period), treatment, and treatment by time interaction as fixed effects, and participant as a random effect. Log-transformed number of days in which seizures were reported by period is included as an offset. Null hypothesis was that the ratio of GWP42003-P to placebo would be 1.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0095</p_value>
            <method>Negative binomial regression</method>
            <param_type>Treatment Ratio</param_type>
            <param_value>0.702</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.538</ci_lower_limit>
            <ci_upper_limit>0.916</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change In Total Seizures During The Treatment Period Compared To Baseline</title>
        <description>Total seizures were defined as the combination of convulsive and non-convulsive seizures. Convulsive seizures were defined as tonic-clonic, tonic, clonic, or atonic seizures. Non-convulsive seizures were defined as myoclonic, countable partial, other partial, or absence seizures. Participants or their caregivers recorded the number and type of convulsive seizures and non-convulsive seizures each day from screening until completion of dosing using an IVRS diary. Change compared to baseline was calculated as per the primary outcome measure. Data reported as the ratio of geometric least squares mean in total seizures and expressed as a percentage reduction.</description>
        <time_frame>Baseline to Day 99 or ET</time_frame>
        <population>Intention-to-treat (ITT) analysis set: All participants who were randomized and dosed in the trial and had post-baseline efficacy data.</population>
        <group_list>
          <group group_id="O1">
            <title>10 mg/kg/Day GWP42003-P</title>
            <description>GWP42003-P oral solution (100 mg/mL cannabidiol in sesame oil with anhydrous ethanol with added sweetener [sucralose] and strawberry flavoring). The 10 mg/kg/day dose was defined as 50% of the 10 mg/kg/day dose.</description>
          </group>
          <group group_id="O2">
            <title>20 mg/kg/Day GWP42003-P</title>
            <description>GWP42003-P oral solution (100 mg/mL cannabidiol in sesame oil with anhydrous ethanol with added sweetener [sucralose] and strawberry flavoring). The 20 mg/kg/day dose was recommended by the DSMC after assessment of safety and pharmacokinetic data from Part A of study GWEP1332 (NCT02091206).</description>
          </group>
          <group group_id="O3">
            <title>Placebo Control</title>
            <description>Excipients only. Participants were pooled from 2 placebo cohorts, half receiving 10 mg/kg/day dose-volume equivalent and half receiving 20 mg/kg/day dose-volume equivalent.</description>
          </group>
        </group_list>
        <measure>
          <title>Change In Total Seizures During The Treatment Period Compared To Baseline</title>
          <description>Total seizures were defined as the combination of convulsive and non-convulsive seizures. Convulsive seizures were defined as tonic-clonic, tonic, clonic, or atonic seizures. Non-convulsive seizures were defined as myoclonic, countable partial, other partial, or absence seizures. Participants or their caregivers recorded the number and type of convulsive seizures and non-convulsive seizures each day from screening until completion of dosing using an IVRS diary. Change compared to baseline was calculated as per the primary outcome measure. Data reported as the ratio of geometric least squares mean in total seizures and expressed as a percentage reduction.</description>
          <population>Intention-to-treat (ITT) analysis set: All participants who were randomized and dosed in the trial and had post-baseline efficacy data.</population>
          <units>percentage reduction</units>
          <param>Geometric Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="66"/>
                <count group_id="O2" value="67"/>
                <count group_id="O3" value="65"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="56.4" lower_limit="47.8" upper_limit="63.6"/>
                    <measurement group_id="O2" value="47.3" lower_limit="36.9" upper_limit="56.0"/>
                    <measurement group_id="O3" value="29.7" lower_limit="16.0" upper_limit="41.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Model includes total number of seizures as a response variable and age group, time (baseline and treatment period), treatment, and treatment by time interaction as fixed effects, and participant as a random effect. Log-transformed number of days in which seizures were reported by period is included as an offset.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0255</p_value>
            <method>Negative binomial regression</method>
            <param_type>Treatment Ratio</param_type>
            <param_value>0.749</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.581</ci_lower_limit>
            <ci_upper_limit>0.965</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Model includes total number of seizures as a response variable and age group, time (baseline and treatment period), treatment, and treatment by time interaction as fixed effects, and participant as a random effect. Log-transformed number of days in which seizures were reported by period is included as an offset.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0003</p_value>
            <method>Negative binomial regression</method>
            <param_type>Treatment Ratio</param_type>
            <param_value>0.620</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.481</ci_lower_limit>
            <ci_upper_limit>0.799</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Participants With A ≥50% Reduction From Baseline In Convulsive Seizure Frequency During The Treatment Period</title>
        <description>Convulsive seizures were defined as tonic-clonic, tonic, clonic, or atonic. Participants or their caregivers recorded the number and type of convulsive seizures each day from screening until completion of dosing using an IVRS diary. Baseline included all available data prior to Day 1 (28-day average). Percentage change from baseline was calculated as: ([frequency during the treatment period - frequency during baseline]/frequency during baseline) x 100. The frequency during each period was based on 28-day averages and calculated as: (number of seizures in the period/number of reported days in the IVRS period) x 28. Baseline included all available data prior to Day 1 (28-day average).</description>
        <time_frame>Baseline to Day 99 or ET</time_frame>
        <population>Intention-to-treat (ITT) analysis set: All participants who were randomized and dosed in the trial and had post-baseline efficacy data.</population>
        <group_list>
          <group group_id="O1">
            <title>10 mg/kg/Day GWP42003-P</title>
            <description>GWP42003-P oral solution (100 mg/mL cannabidiol in sesame oil with anhydrous ethanol with added sweetener [sucralose] and strawberry flavoring). The 10 mg/kg/day dose was defined as 50% of the 10 mg/kg/day dose.</description>
          </group>
          <group group_id="O2">
            <title>20 mg/kg/Day GWP42003-P</title>
            <description>GWP42003-P oral solution (100 mg/mL cannabidiol in sesame oil with anhydrous ethanol with added sweetener [sucralose] and strawberry flavoring). The 20 mg/kg/day dose was recommended by the DSMC after assessment of safety and pharmacokinetic data from Part A of study GWEP1332 (NCT02091206).</description>
          </group>
          <group group_id="O3">
            <title>Placebo Control</title>
            <description>Excipients only. Participants were pooled from 2 placebo cohorts, half receiving 10 mg/kg/day dose-volume equivalent and half receiving 20 mg/kg/day dose-volume equivalent.</description>
          </group>
        </group_list>
        <measure>
          <title>Participants With A ≥50% Reduction From Baseline In Convulsive Seizure Frequency During The Treatment Period</title>
          <description>Convulsive seizures were defined as tonic-clonic, tonic, clonic, or atonic. Participants or their caregivers recorded the number and type of convulsive seizures each day from screening until completion of dosing using an IVRS diary. Baseline included all available data prior to Day 1 (28-day average). Percentage change from baseline was calculated as: ([frequency during the treatment period - frequency during baseline]/frequency during baseline) x 100. The frequency during each period was based on 28-day averages and calculated as: (number of seizures in the period/number of reported days in the IVRS period) x 28. Baseline included all available data prior to Day 1 (28-day average).</description>
          <population>Intention-to-treat (ITT) analysis set: All participants who were randomized and dosed in the trial and had post-baseline efficacy data.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="66"/>
                <count group_id="O2" value="67"/>
                <count group_id="O3" value="65"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29"/>
                    <measurement group_id="O2" value="33"/>
                    <measurement group_id="O3" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0069</p_value>
            <method>Cochran-Mantel-Haenszel</method>
            <method_desc>P-value calculated from a Cochran-Mantel-Haenszel test stratified by age group (2-5, 6-12, and 13-18 years).</method_desc>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>2.74</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.32</ci_lower_limit>
            <ci_upper_limit>5.70</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0332</p_value>
            <method>Cochran-Mantel-Haenszel</method>
            <method_desc>P-value calculated from a Cochran-Mantel-Haenszel test stratified by age group (2-5, 6-12, and 13-18 years).</method_desc>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>2.21</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.06</ci_lower_limit>
            <ci_upper_limit>4.62</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Caregiver Global Impression Of Change (CGIC) At The Last Visit</title>
        <description>On Day 1 (prior to receiving study drug), the caregiver was asked to write a brief description of the participant's overall condition as a memory aid for the CGIC questionnaire at subsequent visits. The CGIC questionnaire comprised the following question, to be rated on a 7-point scale: Since your child started treatment, please assess the status of your child's overall condition (comparing their condition now to their condition before treatment) using the scale below. The markers were: &quot;Very Much Improved&quot;; &quot;Much Improved&quot;; &quot;Slightly Improved&quot;; &quot;No Change&quot;; &quot;Slightly Worse&quot;; &quot;Much Worse&quot;; &quot;Very Much Worse&quot;. The CGIC response/score, recorded at each visit, was summarized, on both a categorical and continuous scale, by treatment group. The scores at the last scheduled visit (not including the end of taper or safety follow-up visits) at which participant's last evaluation was performed were analyzed using ordinal logistic regression.</description>
        <time_frame>Baseline to Last Visit</time_frame>
        <population>Intention-to-treat (ITT) analysis set: All participants who were randomized and dosed in the trial and had post-baseline efficacy data.</population>
        <group_list>
          <group group_id="O1">
            <title>10 mg/kg/Day GWP42003-P</title>
            <description>GWP42003-P oral solution (100 mg/mL cannabidiol in sesame oil with anhydrous ethanol with added sweetener [sucralose] and strawberry flavoring). The 10 mg/kg/day dose was defined as 50% of the 10 mg/kg/day dose.</description>
          </group>
          <group group_id="O2">
            <title>20 mg/kg/Day GWP42003-P</title>
            <description>GWP42003-P oral solution (100 mg/mL cannabidiol in sesame oil with anhydrous ethanol with added sweetener [sucralose] and strawberry flavoring). The 20 mg/kg/day dose was recommended by the DSMC after assessment of safety and pharmacokinetic data from Part A of study GWEP1332 (NCT02091206).</description>
          </group>
          <group group_id="O3">
            <title>Placebo Control</title>
            <description>Excipients only. Participants were pooled from 2 placebo cohorts, half receiving 10 mg/kg/day dose-volume equivalent and half receiving 20 mg/kg/day dose-volume equivalent.</description>
          </group>
        </group_list>
        <measure>
          <title>Caregiver Global Impression Of Change (CGIC) At The Last Visit</title>
          <description>On Day 1 (prior to receiving study drug), the caregiver was asked to write a brief description of the participant's overall condition as a memory aid for the CGIC questionnaire at subsequent visits. The CGIC questionnaire comprised the following question, to be rated on a 7-point scale: Since your child started treatment, please assess the status of your child's overall condition (comparing their condition now to their condition before treatment) using the scale below. The markers were: &quot;Very Much Improved&quot;; &quot;Much Improved&quot;; &quot;Slightly Improved&quot;; &quot;No Change&quot;; &quot;Slightly Worse&quot;; &quot;Much Worse&quot;; &quot;Very Much Worse&quot;. The CGIC response/score, recorded at each visit, was summarized, on both a categorical and continuous scale, by treatment group. The scores at the last scheduled visit (not including the end of taper or safety follow-up visits) at which participant's last evaluation was performed were analyzed using ordinal logistic regression.</description>
          <population>Intention-to-treat (ITT) analysis set: All participants who were randomized and dosed in the trial and had post-baseline efficacy data.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="66"/>
                <count group_id="O2" value="66"/>
                <count group_id="O3" value="65"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Very Much Improved</title>
                  <measurement_list>
                    <measurement group_id="O1" value="13"/>
                    <measurement group_id="O2" value="11"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Much Improved</title>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                    <measurement group_id="O2" value="10"/>
                    <measurement group_id="O3" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Slightly Improved</title>
                  <measurement_list>
                    <measurement group_id="O1" value="21"/>
                    <measurement group_id="O2" value="19"/>
                    <measurement group_id="O3" value="18"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No Change</title>
                  <measurement_list>
                    <measurement group_id="O1" value="18"/>
                    <measurement group_id="O2" value="17"/>
                    <measurement group_id="O3" value="32"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Slightly Worse</title>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="5"/>
                    <measurement group_id="O3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Much Worse</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Very Much Worse</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0279</p_value>
            <method>Regression, Logistic</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>2.02</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.08</ci_lower_limit>
            <ci_upper_limit>3.78</ci_upper_limit>
            <estimate_desc>Proportional odds modelling was carried out by including treatment group as a fixed factor. The estimated OR tested the null hypothesis that OR was equal to 1.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0009</p_value>
            <method>Regression, Logistic</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>2.93</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.56</ci_lower_limit>
            <ci_upper_limit>5.53</ci_upper_limit>
            <estimate_desc>Proportional odds modelling was carried out by including treatment group as a fixed factor. The estimated OR tested the null hypothesis that OR was equal to 1.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From Day 1 to Day 137.</time_frame>
      <desc>Safety Analysis Set: Received at least 1 dose of study drug and were analyzed per treatment received. Two participants randomized to receive GWP42003-P 10 mg/kg/day titrated above the target dose and were therefore assigned to the GWP42003-P 20 mg/kg/day group for all safety analyses.</desc>
      <group_list>
        <group group_id="E1">
          <title>10 mg/kg/Day GWP42003-P</title>
          <description>GWP42003-P oral solution (100 mg/mL cannabidiol in sesame oil with anhydrous ethanol with added sweetener [sucralose] and strawberry flavoring). The 10 mg/kg/day dose was defined as 50% of the 10 mg/kg/day dose.</description>
        </group>
        <group group_id="E2">
          <title>20 mg/kg/Day GWP42003-P</title>
          <description>GWP42003-P oral solution (100 mg/mL cannabidiol in sesame oil with anhydrous ethanol with added sweetener [sucralose] and strawberry flavoring). The 20 mg/kg/day dose was recommended by the DSMC after assessment of safety and pharmacokinetic data from Part A of study GWEP1332 (NCT02091206).</description>
        </group>
        <group group_id="E3">
          <title>Placebo Control</title>
          <description>Excipients only. Participants were pooled from 2 placebo cohorts, half receiving 10 mg/kg/day dose-volume equivalent and half receiving 20 mg/kg/day dose-volume equivalent.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 17.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="69"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="17" subjects_at_risk="69"/>
                <counts group_id="E3" subjects_affected="10" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="69"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="69"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Drug interaction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="69"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="69"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="69"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Viral infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="69"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Coxsackie viral infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="69"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="69"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="69"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Adenovirus infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="69"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Laryngitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="69"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="69"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Viral upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="69"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Toxicity to various agents</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="69"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="65"/>
              </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="64"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="69"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="69"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Liver function test abnormal</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="69"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="65"/>
              </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="1" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="69"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Status epilepticus</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="69"/>
                <counts group_id="E3" subjects_affected="8" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Generalised tonic-clonic seizure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="69"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Convulsion</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="69"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="69"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Seizure cluster</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="69"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Unresponsive to stimuli</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="69"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Psychogenic seizure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="69"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Respiratory depression</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="69"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Respiratory distress</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="69"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Pneumonia aspiration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="69"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="65"/>
              </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="0" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="69"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 17.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="56" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="60" subjects_at_risk="69"/>
                <counts group_id="E3" subjects_affected="58" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="18" subjects_at_risk="69"/>
                <counts group_id="E3" subjects_affected="8" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="69"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="69"/>
                <counts group_id="E3" subjects_affected="11" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="69"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="69"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="69"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="69"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Toxicity to various agents</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="69"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="69"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="69"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Gamma-glutamyltransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="69"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="65"/>
              </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="10" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="19" subjects_at_risk="69"/>
                <counts group_id="E3" subjects_affected="11" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="16" subjects_at_risk="69"/>
                <counts group_id="E3" subjects_affected="9" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Convulsion</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="69"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Tremor</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="69"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Aggression</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="69"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Irritability</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="69"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Abnormal behaviour</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="69"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="69"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Medical Enquiries</name_or_title>
      <organization>GW Research Ltd</organization>
      <phone>+44 01223 238170; +18778862810</phone>
      <email>medinfo@gwpharm.com; medinfo@greenwichbiosciences.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/NCT02224703
org study id: GWEP1424
secondary id: 2014-002939-34
nct id: NCT02224703
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
To investigate the potential antiepileptic effects of cannabidiol (GWP42003-P) in children
      and young adults with Dravet syndrome.
This study was a 2:2:1:1 randomized, double-blind, 14-week comparison of two dose levels of
      GWP42003-P (10 milligram/kilogram [mg/kg]/day and 20 mg/kg/day) versus placebo (10 mg/kg/day
      dose-volume equivalent and 20 mg/kg/day dose-volume equivalent; presented as pooled placebo
      in the study). A 28-day screening period prior to randomization (to establish baseline
      parameters) preceded the treatment period, which consisted of a 2-week titration period
      followed by a 12-week maintenance period. The study aimed to determine the efficacy, safety,
      and tolerability of GWP42003-P compared with placebo. 20 mg/kg/day was recommended by the
      Data Safety Monitoring Committee (DSMC) after assessment of safety and pharmacokinetic data
      from Part A of study GWEP1332 (NCT02091206). The first participant did not enroll into this
      study until the DSMC reviewed the safety data from Part A of study GWEP1332 (NCT02091206).

      Following study completion, all participants were invited to continue to receive GWP42003-P
      in a separate open-label extension study (GWEP1415; NCT02224573).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change In Convulsive Seizures During The Treatment Period Compared To Baseline
time frame: Baseline to Day 99 or Early Termination (ET)
description: Convulsive seizures were defined as tonic-clonic, tonic, clonic, or atonic. Participants or their caregivers recorded the number and type of convulsive seizures each day from screening until completion of dosing using an interactive voice response system (IVRS) diary. The primary endpoint was analyzed using negative binomial regression on the sum of the convulsive seizure counts during the treatment period, based on the ITT analysis set. Baseline included all available data prior to Day 1. Data reported as the ratio of geometric least squares mean in convulsive seizures and expressed as a percentage reduction.
measure: Change In Total Seizures During The Treatment Period Compared To Baseline
time frame: Baseline to Day 99 or ET
description: Total seizures were defined as the combination of convulsive and non-convulsive seizures. Convulsive seizures were defined as tonic-clonic, tonic, clonic, or atonic seizures. Non-convulsive seizures were defined as myoclonic, countable partial, other partial, or absence seizures. Participants or their caregivers recorded the number and type of convulsive seizures and non-convulsive seizures each day from screening until completion of dosing using an IVRS diary. Change compared to baseline was calculated as per the primary outcome measure. Data reported as the ratio of geometric least squares mean in total seizures and expressed as a percentage reduction.
measure: Participants With A ≥50% Reduction From Baseline In Convulsive Seizure Frequency During The Treatment Period
time frame: Baseline to Day 99 or ET
description: Convulsive seizures were defined as tonic-clonic, tonic, clonic, or atonic. Participants or their caregivers recorded the number and type of convulsive seizures each day from screening until completion of dosing using an IVRS diary. Baseline included all available data prior to Day 1 (28-day average). Percentage change from baseline was calculated as: ([frequency during the treatment period - frequency during baseline]/frequency during baseline) x 100. The frequency during each period was based on 28-day averages and calculated as: (number of seizures in the period/number of reported days in the IVRS period) x 28. Baseline included all available data prior to Day 1 (28-day average).
measure: Caregiver Global Impression Of Change (CGIC) At The Last Visit
time frame: Baseline to Last Visit
description: On Day 1 (prior to receiving study drug), the caregiver was asked to write a brief description of the participant's overall condition as a memory aid for the CGIC questionnaire at subsequent visits. The CGIC questionnaire comprised the following question, to be rated on a 7-point scale: Since your child started treatment, please assess the status of your child's overall condition (comparing their condition now to their condition before treatment) using the scale below. The markers were: "Very Much Improved"; "Much Improved"; "Slightly Improved"; "No Change"; "Slightly Worse"; "Much Worse"; "Very Much Worse". The CGIC response/score, recorded at each visit, was summarized, on both a categorical and continuous scale, by treatment group. The scores at the last scheduled visit (not including the end of taper or safety follow-up visits) at which participant's last evaluation was performed were analyzed using ordinal logistic regression.
arm group label: 10 mg/kg/day GWP42003-P
arm group type: Experimental
description: GWP42003-P oral solution (100 mg/milliliter [mL] cannabidiol in sesame oil with anhydrous ethanol with added sweetener [sucralose] and strawberry flavoring). The 10 mg/kg/day dose was defined as 50% of the 20 mg/kg/day dose.
arm group label: 20 mg/kg/day GWP42003-P
arm group type: Experimental
description: GWP42003-P oral solution (100 mg/mL cannabidiol in sesame oil with anhydrous ethanol with added sweetener [sucralose] and strawberry flavoring). The 20 mg/kg/day dose was recommended by the DSMC after assessment of safety and pharmacokinetic data from Part A of study GWEP1332 (NCT02091206).
arm group label: Placebo Control
arm group type: Placebo Comparator
description: Excipients only. Participants were pooled from 2 placebo cohorts, half receiving 10 mg/kg/day dose-volume equivalent and half receiving 20 mg/kg/day dose-volume equivalent.
intervention type: Drug
intervention name: GWP42003-P
arm group label: 10 mg/kg/day GWP42003-P
arm group label: 20 mg/kg/day GWP42003-P
other name: Cannabidiol
other name: CBD
other name: Epidiolex
intervention type: Drug
intervention name: Placebo Control
arm group label: Placebo Control
other name: Placebo
criteria: 
gender: All
minimum age: 2 Years
maximum age: 18 Years
healthy volunteers: No
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country: Australia
country: Israel
country: Netherlands
country: Poland
country: Spain
country: United States
responsible party type: Sponsor
mesh term: Epilepsies, Myoclonic
mesh term: Syndrome
mesh term: Cannabidiol
provided document: 
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certain agreements: 
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