<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/NCT02224560</url>
  </required_header>
  <id_info>
    <org_study_id>GWEP1414</org_study_id>
    <secondary_id>2014-002940-42</secondary_id>
    <nct_id>NCT02224560</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety of GWP42003-P for Seizures Associated With Lennox-Gastaut Syndrome in Children and Adults</brief_title>
  <acronym>GWPCARE3</acronym>
  <official_title>A Randomized, Double-blind, Placebo-controlled Study to Investigate the Efficacy and Safety of Cannabidiol (GWP42003-P; CBD) as Adjunctive Treatment for Seizures Associated With Lennox-Gastaut Syndrome in Children and Adults.</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objective of this study was to evaluate the efficacy of GWP42003-P as adjunctive&#xD;
      treatment in reducing the number of drop seizures when compared with placebo in participants&#xD;
      with Lennox-Gastaut syndrome (LGS).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study was a 1:1:1 randomized, double-blind, 14-week comparison of 2 dose levels (10&#xD;
      milligram [mg] per kilogram [kg] per day [mg/kg/day] and 20 mg/kg/day) of GWP42003-P versus&#xD;
      placebo. Participants who satisfied all inclusion and none of the exclusion criteria began a&#xD;
      28-day baseline observation period. The treatment period consisted of a 2-week titration&#xD;
      period followed by a 12-week maintenance period. The 20 mg/kg/day dose 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 10 mg/kg/day dose was defined as 50% of the&#xD;
      20 mg/kg/day dose. The first participant was not enrolled into this study until the DSMC had&#xD;
      reviewed the safety data from Part A of study GWEP1332.&#xD;
&#xD;
      Participants who satisfied all eligibility criteria were randomized at Day 1 to receive 10&#xD;
      mg/kg/day GWP42003-P, 20 mg/kg/day GWP42003-P, or placebo at a 1:1:1 ratio. Participants in&#xD;
      the placebo group were split into 2 equivalent cohorts; one half received 10 mg/kg/day dosing&#xD;
      volumes and one half received 20 mg/kg/day dosing volumes. The 2 placebo cohorts were pooled&#xD;
      for the analyses of efficacy. Participants titrated GWP42003-P to the 10 mg/kg/day or 20&#xD;
      mg/kg/day (or equivalent volume of placebo) dose over 7 and 11 days, respectively, and&#xD;
      remained at this dose for the 12-week maintenance period. Following the end of treatment (Day&#xD;
      99), participants were invited to continue to receive GWP42003-P in an open-label extension&#xD;
      (OLE) study under a separate protocol (GWEP1415; NCT02224573). All participants who did not&#xD;
      immediately enter the OLE study tapered investigational medicinal product (IMP) (10% per day&#xD;
      over 10 days). However, the taper period could be interrupted if the participant wished to&#xD;
      enter the OLE study within a 7-day timeframe. Participants who down-titrated IMP returned for&#xD;
      an end of taper period visit (Day 109). Participants who did not enter the OLE study or who&#xD;
      withdrew prematurely had a safety follow-up visit 28 days later (Day 137).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 8, 2015</start_date>
  <completion_date type="Actual">May 19, 2016</completion_date>
  <primary_completion_date type="Actual">May 19, 2016</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>Percentage Change From Baseline In Drop Seizure Frequency During The Treatment Period</measure>
    <time_frame>Baseline to End of Treatment (EOT) (Day 99) or Early Termination (ET)</time_frame>
    <description>Drop seizures were recorded by the participant or caregiver using an interactive voice response system (IVRS) diary. Drop seizures were defined as the subset of tonic-clonic, tonic or atonic seizures that were reported as drop seizures in the IVRS. 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). Negative percentages show an improvement from baseline.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number Of Participants With A ≥50% Reduction From Baseline In Drop Seizure Frequency During The Treatment Period</measure>
    <time_frame>Baseline to EOT (Day 99) or ET</time_frame>
    <description>Drop seizures were recorded by the participant or caregiver using an IVRS diary. Drop seizures included the subset of tonic-clonic, tonic, or atonic seizures that were reported as drop seizures in IVRS. Percentage change from baseline was calculated as per the primary outcome measure.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage Change From Baseline In Total Seizure Frequency During The Treatment Period</measure>
    <time_frame>Baseline to EOT (Day 99) or ET</time_frame>
    <description>Total seizures included the sum of all seizures (tonic-clonic, tonic, atonic, clonic, myoclonic, countable partial, other partial, and absence seizures) recorded by the participant or caregiver using an IVRS diary. Percentage change from baseline was calculated as per the primary outcome measure. Negative percentages show an improvement from baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Subject/Caregiver Global Impression Of Change (S/CGIC) Assessment</measure>
    <time_frame>Baseline to Last Visit (Day 99) or ET</time_frame>
    <description>The S/CGIC was used to assess the participant's overall condition on a 7-point scale, using the markers &quot;very much improved, much improved, slightly improved, no change, slightly worse, much worse, or very much worse&quot; (1 = very much improved; 7 = very much worse). On Day 1 (prior to starting IMP), the caregiver was asked to write a brief description of the participant's overall condition as a memory aid for the S/CGIC questionnaire at subsequent visits. If both a CGIC and SGIC were completed then the CGIC was used; if only a CGIC was completed then the CGIC was used; if only a SGIC was completed then the SGIC was used. Last visit for endpoints assessed at clinic visits was defined as the last scheduled visit (not including the end of taper or safety follow-up visits) at which participant's last evaluation was performed.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">225</enrollment>
  <condition>Epilepsy</condition>
  <condition>Lennox Gastaut Syndrome</condition>
  <arm_group>
    <arm_group_label>GWP42003-P 20 mg/kg/day Dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received GWP42003-P 20 mg/kg/day administered orally, half in the morning and half in the evening. Participants titrated GWP42003-P to 20 mg/kg/day over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day) period.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>GWP42003-P 10 mg/kg/day Dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received GWP42003-P 10 mg/kg/day administered orally, half in the morning and half in the evening. Participants titrated GWP42003-P to 10 mg/kg/day over 7 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day) period.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants received placebo (0 mg/mL CBD) volume matched to 1 of the 2 dose levels (10 or 20 mg/kg/day) administered orally, half in the morning and half in the evening. To maintain the blinded aspect of the study, participants titrated the placebo dose over 7 to 11 days according to the matched IMP group (7 or 11 days for the 10 or 20 mg/kg/day GWP42003-P groups, respectively) and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day of the matched dose) period.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>GWP42003-P</intervention_name>
    <description>GWP42003-P was presented as an oral solution containing 100 mg/milliliter (mL) cannabidiol (CBD) in the excipients sesame oil and anhydrous ethanol (79 mg/mL) with added sweetener (0.5 mg/mL sucralose) and strawberry flavoring (0.2 mg/mL). Participants were randomly assigned to receive either 10 or 20 mg/kg/day.</description>
    <arm_group_label>GWP42003-P 10 mg/kg/day Dose</arm_group_label>
    <arm_group_label>GWP42003-P 20 mg/kg/day Dose</arm_group_label>
    <other_name>Cannabidiol</other_name>
    <other_name>Epidiolex</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo control</intervention_name>
    <description>Placebo was presented as an oral solution containing 0 mg/mL CBD in the excipients sesame oil and anhydrous ethanol (79 mg/mL) with added sweetener (0.5 mg/mL sucralose) and strawberry flavoring (0.2 mg/mL).</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>Placebo</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria:&#xD;
&#xD;
          -  Participant and/or parent(s)/legal representatives were willing and able to give&#xD;
             informed assent/consent for participation in the study.&#xD;
&#xD;
          -  Participant and his or her caregivers were willing and able (in the investigator's&#xD;
             opinion) to comply with all study requirements.&#xD;
&#xD;
          -  Participant was male or female aged between 2 and 55 years (inclusive).&#xD;
&#xD;
          -  Participant had a documented history of LGS. This included written documentation of&#xD;
             having met electroencephalogram (EEG) diagnostic criteria during the participant's&#xD;
             history and evidence of at least 1 type of generalized seizure, including drop&#xD;
             seizures (atonic, tonic, tonic-clonic or myoclonic) for at least 6 months.&#xD;
&#xD;
          -  Participant had a history of slow (&lt;3.0 hertz [Hz]) spike-and-wave pattern in an EEG&#xD;
             prior to the enrollment into the baseline period.&#xD;
&#xD;
          -  Participant had at least 2 drop seizures each week during the first 28 days of the&#xD;
             baseline period.&#xD;
&#xD;
          -  Participant was refractory; that is having documented failures on more than 1&#xD;
             antiepileptic drug (AED).&#xD;
&#xD;
          -  Participant was taking 1 or more AEDs at a dose which had been stable for at least 4&#xD;
             weeks prior to screening.&#xD;
&#xD;
          -  All medications or interventions for epilepsy (including ketogenic diet and vagus&#xD;
             nerve stimulation [VNS]) were stable for 4 weeks prior to screening and the&#xD;
             participant was willing to maintain a stable regimen throughout the study. The&#xD;
             ketogenic diet and VNS treatments were not counted as an AED.&#xD;
&#xD;
          -  Participant and/or parent(s)/legal representatives were willing to allow his or her&#xD;
             primary care practitioner and consultant to be notified of participation in the study.&#xD;
&#xD;
          -  Participant completed his or her interactive voice response (IVRS) telephone diary on&#xD;
             at least 25 days of the baseline period.&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
          -  Etiology of participant's seizures was a progressive neurologic disease. Participants&#xD;
             with tuberous sclerosis were not excluded from study participation, unless there was a&#xD;
             progressive tumor.&#xD;
&#xD;
          -  Participant had an anoxic episode requiring resuscitation within 6 months of&#xD;
             screening.&#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 had a history or presence of alcohol or substance abuse within the last 2&#xD;
             years prior to the study or daily consumption of 5 or more alcohol-containing&#xD;
             beverages.&#xD;
&#xD;
          -  Participant was currently using or had in the past used recreational or medicinal&#xD;
             cannabis, or synthetic cannabinoid-based medications (including Sativex®) within the 3&#xD;
             months prior to study entry and was unwilling to abstain for the duration of the&#xD;
             study.&#xD;
&#xD;
          -  Participant had a history of symptoms (for example, dizziness, light-headedness,&#xD;
             blurred vision, palpitations, weakness, syncope) related to a drop in blood pressure&#xD;
             due to postural changes.&#xD;
&#xD;
          -  Participant had any known or suspected hypersensitivity to cannabinoids or any of the&#xD;
             excipients of the IMP, such as sesame oil.&#xD;
&#xD;
          -  Female participant was of child bearing potential or male participant's partner was of&#xD;
             child bearing potential; unless willing to ensure that they or their partner used a&#xD;
             highly effective method of contraception for the duration of the study and for 3&#xD;
             months thereafter.&#xD;
&#xD;
          -  Female participant was pregnant (positive pregnancy test), lactating or planning&#xD;
             pregnancy during the course of the study and for 3 months thereafter.&#xD;
&#xD;
          -  Participant had been part of a clinical study involving another IMP in the previous 6&#xD;
             months.&#xD;
&#xD;
          -  Patient had significantly impaired hepatic function at screening (Day -28) or&#xD;
             randomization (Day 1), defined as any of the following: alanine aminotransferase (ALT)&#xD;
             or aspartate aminotransferase (AST) &gt; 5 × upper limit of normal (ULN); ALT or AST &gt; 3&#xD;
             × ULN and total bilirubin &gt; 2 × ULN or international normalized ratio (INR) &gt; 1.5; ALT&#xD;
             or AST &gt; 3 × ULN with the presence of fatigue, nausea, vomiting, right upper quadrant&#xD;
             pain or tenderness, fever, rash, and/or eosinophilia (&gt;5%). This criterion could only&#xD;
             be confirmed once the laboratory results were available; participants randomized into&#xD;
             the study who were later found not to meet this criterion were withdrawn from the&#xD;
             study.&#xD;
&#xD;
          -  Any history of suicidal behavior or any suicidal ideation of type 4 or 5 on the&#xD;
             Columbia Suicide Severity Rating Scale in the last month or at screening.&#xD;
&#xD;
          -  Participant was unwilling to abstain from donation of blood during the study.&#xD;
&#xD;
          -  Participant planned to travel outside his or her country of residence during the&#xD;
             study.&#xD;
&#xD;
          -  Participant had previously randomized into the study.&#xD;
&#xD;
          -  Participant was taking more than 4 concurrent AEDs.&#xD;
&#xD;
          -  Participant had taken corticotropins in the 6 months prior to screening.&#xD;
&#xD;
          -  Participant was currently taking long-term systemic steroids (excluding inhaled&#xD;
             medication for asthma treatment) or any other daily medication known to exacerbate&#xD;
             epilepsy. An exception was made of prophylactic medication, for example, idiopathic&#xD;
             nephrotic syndrome or asthma.&#xD;
&#xD;
          -  Participant was taking felbamate, and he or she had been taking it for less than 1&#xD;
             year prior to screening.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>2 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35294</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85054</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>Hartford</city>
        <state>Connecticut</state>
        <zip>06106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32819</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Augusta</city>
        <state>Georgia</state>
        <zip>30912</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Boise</city>
        <state>Idaho</state>
        <zip>83702</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Buffalo</city>
        <state>New York</state>
        <zip>14222</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10003</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Clemmons</city>
        <state>North Carolina</state>
        <zip>27012</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Winston-Salem</city>
        <state>North Carolina</state>
        <zip>27157</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45267</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>York</city>
        <state>Pennsylvania</state>
        <zip>17403</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>Charlottesville</city>
        <state>Virginia</state>
        <zip>22903</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Paris</city>
        <zip>75015</zip>
        <country>France</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>28034</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Pamplona</city>
        <zip>31080</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>
    <facility>
      <address>
        <city>Edinburgh</city>
        <zip>EH9 1LF</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Glasgow</city>
        <zip>G51 4TF</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>London</city>
        <zip>WC1N 3JH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
    <country>Spain</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <results_reference>
    <citation>Devinsky O, Patel AD, Cross JH, Villanueva V, Wirrell EC, Privitera M, Greenwood SM, Roberts C, Checketts D, VanLandingham KE, Zuberi SM; GWPCARE3 Study Group. Effect of Cannabidiol on Drop Seizures in the Lennox-Gastaut Syndrome. N Engl J Med. 2018 May 17;378(20):1888-1897. doi: 10.1056/NEJMoa1714631.</citation>
    <PMID>29768152</PMID>
  </results_reference>
  <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>June 25, 2018</results_first_submitted>
  <results_first_submitted_qc>July 26, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">July 27, 2018</results_first_posted>
  <disposition_first_submitted>September 18, 2017</disposition_first_submitted>
  <disposition_first_submitted_qc>September 18, 2017</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">September 26, 2017</disposition_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>Epidiolex</keyword>
  <keyword>GWP42003-P</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Seizures</mesh_term>
    <mesh_term>Lennox Gastaut Syndrome</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cannabidiol</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>The dose levels of 10 and 20 milligram (mg) per kilogram (kg) per day (mg/kg/day) were recommended by the Data Safety Monitoring Committee (DSMC) of study GWEP1332 Part A (NCT02091206) after assessment of safety and pharmacokinetic data. Participants of GWEP1414 were not enrolled until the DSMC had reviewed the safety data of GWEP1332 Part A.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>GWP42003-P 20 mg/kg/Day Dose</title>
          <description>Participants received GWP42003-P 20 mg/kg/day administered orally, half in the morning and half in the evening. Participants titrated GWP42003-P to 20 mg/kg/day over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the open-label extension (OLE) study, the maintenance period was followed by a 10-day taper (10% per day) period.</description>
        </group>
        <group group_id="P2">
          <title>GWP42003-P 10 mg/kg/Day Dose</title>
          <description>Participants received GWP42003-P 10 mg/kg/day administered orally, half in the morning and half in the evening. Participants titrated GWP42003-P to 10 mg/kg/day over 7 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day) period.</description>
        </group>
        <group group_id="P3">
          <title>Placebo</title>
          <description>Participants received placebo (0 mg/milliliter [mL] cannabidiol [CBD]), volume matched to 1 of the 2 dose levels (10 or 20 mg/kg/day), administered orally, half in the morning and half in the evening. To maintain the blinded aspect of the study, participants titrated the placebo dose over 7 to 11 days according to the matched investigational medicinal product (IMP) group (7 or 11 days for the 10 or 20 mg/kg/day GWP42003-P groups, respectively) and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day of the matched dose) period.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="76"/>
                <participants group_id="P2" count="73"/>
                <participants group_id="P3" count="76"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Safety Analysis Set</title>
              <participants_list>
                <participants group_id="P1" count="82">Six participants assigned to the 10 mg/kg/day dose were included in the 20 mg/kg/day group.</participants>
                <participants group_id="P2" count="67">Six participants assigned to the 10 mg/kg/day dose were included in the 20 mg/kg/day group.</participants>
                <participants group_id="P3" count="76"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Intent to Treat (ITT) Analysis Set</title>
              <participants_list>
                <participants group_id="P1" count="76"/>
                <participants group_id="P2" count="73"/>
                <participants group_id="P3" count="76"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="67"/>
                <participants group_id="P2" count="71"/>
                <participants group_id="P3" count="74"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Protocol Deviation</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>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Met Withdrawal Criteria</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>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
              </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="1"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>ITT Analysis Set: Received at least 1 dose of IMP with at least 1 post-baseline efficacy endpoint measurement. Participants were analyzed according to the treatment group to which they were randomized.</population>
      <group_list>
        <group group_id="B1">
          <title>GWP42003-P 20 mg/kg/Day Dose-ITT Analysis Set</title>
          <description>Participants received at least 1 dose of IMP with at least 1 post-baseline efficacy endpoint measurement; analyzed according to the treatment group to which they were randomized (GWP42003-P 20 mg/kg/day).</description>
        </group>
        <group group_id="B2">
          <title>GWP42003-P 10 mg/kg/Day Dose-ITT Analysis Set</title>
          <description>Participants received at least 1 dose of IMP with at least 1 post-baseline efficacy endpoint measurement; analyzed according to the treatment group to which they were randomized (GWP42003-P 10 mg/kg/day).</description>
        </group>
        <group group_id="B3">
          <title>Placebo-ITT Analysis Set</title>
          <description>Participants received at least 1 dose of IMP with at least 1 post-baseline efficacy endpoint measurement; analyzed according to the treatment group to which they were randomized (Placebo).</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="76"/>
            <count group_id="B2" value="73"/>
            <count group_id="B3" value="76"/>
            <count group_id="B4" value="225"/>
          </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="16.0" spread="10.8"/>
                    <measurement group_id="B2" value="15.4" spread="9.5"/>
                    <measurement group_id="B3" value="15.3" spread="9.3"/>
                    <measurement group_id="B4" value="15.6" spread="9.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="31"/>
                    <measurement group_id="B2" value="33"/>
                    <measurement group_id="B3" value="32"/>
                    <measurement group_id="B4" value="96"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="45"/>
                    <measurement group_id="B2" value="40"/>
                    <measurement group_id="B3" value="44"/>
                    <measurement group_id="B4" value="129"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage Change From Baseline In Drop Seizure Frequency During The Treatment Period</title>
        <description>Drop seizures were recorded by the participant or caregiver using an interactive voice response system (IVRS) diary. Drop seizures were defined as the subset of tonic-clonic, tonic or atonic seizures that were reported as drop seizures in the IVRS. 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). Negative percentages show an improvement from baseline.</description>
        <time_frame>Baseline to End of Treatment (EOT) (Day 99) or Early Termination (ET)</time_frame>
        <population>ITT Analysis Set: Received at least 1 dose of IMP with at least 1 post-baseline efficacy endpoint measurement. Participants were analyzed according to the treatment group to which they were randomized.</population>
        <group_list>
          <group group_id="O1">
            <title>GWP42003-P 20 mg/kg/Day Dose</title>
            <description>Participants received GWP42003-P 20 mg/kg/day administered orally, half in the morning and half in the evening. Participants titrated GWP42003-P to 20 mg/kg/day over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day) period.</description>
          </group>
          <group group_id="O2">
            <title>GWP42003-P 10 mg/kg/Day Dose</title>
            <description>Participants received GWP42003-P 10 mg/kg/day administered orally, half in the morning and half in the evening. Participants titrated GWP42003-P to 10 mg/kg/day over 7 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day) period.</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>Participants received placebo (0 mg/mL CBD), volume matched to 1 of the 2 dose levels (10 or 20 mg/kg/day), administered orally, half in the morning and half in the evening. To maintain the blinded aspect of the study, participants titrated the placebo dose over 7 to 11 days according to the matched IMP group (7 or 11 days for the 10 or 20 mg/kg/day GWP42003-P groups, respectively) and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day of the matched dose) period.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage Change From Baseline In Drop Seizure Frequency During The Treatment Period</title>
          <description>Drop seizures were recorded by the participant or caregiver using an interactive voice response system (IVRS) diary. Drop seizures were defined as the subset of tonic-clonic, tonic or atonic seizures that were reported as drop seizures in the IVRS. 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). Negative percentages show an improvement from baseline.</description>
          <population>ITT Analysis Set: Received at least 1 dose of IMP with at least 1 post-baseline efficacy endpoint measurement. Participants were analyzed according to the treatment group to which they were randomized.</population>
          <units>percentage change</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="76"/>
                <count group_id="O2" value="73"/>
                <count group_id="O3" value="76"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-41.86" lower_limit="-72.4" upper_limit="-1.3"/>
                    <measurement group_id="O2" value="-37.16" lower_limit="-63.8" upper_limit="-5.6"/>
                    <measurement group_id="O3" value="-17.17" lower_limit="-37.1" upper_limit="0.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <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>0.0047</p_value>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>-21.57</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-34.79</ci_lower_limit>
            <ci_upper_limit>-6.67</ci_upper_limit>
            <estimate_desc>Calculated using the Hodges-Lehmann approach</estimate_desc>
          </analysis>
          <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>0.0016</p_value>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>-19.19</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-31.24</ci_lower_limit>
            <ci_upper_limit>-7.69</ci_upper_limit>
            <estimate_desc>Calculated using the Hodges-Lehmann approach</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number Of Participants With A ≥50% Reduction From Baseline In Drop Seizure Frequency During The Treatment Period</title>
        <description>Drop seizures were recorded by the participant or caregiver using an IVRS diary. Drop seizures included the subset of tonic-clonic, tonic, or atonic seizures that were reported as drop seizures in IVRS. Percentage change from baseline was calculated as per the primary outcome measure.</description>
        <time_frame>Baseline to EOT (Day 99) or ET</time_frame>
        <population>ITT Analysis Set: Received at least 1 dose of IMP with at least 1 post-baseline efficacy endpoint measurement. Participants were analyzed according to the treatment group to which they were randomized.</population>
        <group_list>
          <group group_id="O1">
            <title>GWP42003-P 20 mg/kg/Day Dose</title>
            <description>Participants received GWP42003-P 20 mg/kg/day administered orally, half in the morning and half in the evening. Participants titrated GWP42003-P to 20 mg/kg/day over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day) period.</description>
          </group>
          <group group_id="O2">
            <title>GWP42003-P 10 mg/kg/Day Dose</title>
            <description>Participants received GWP42003-P 10 mg/kg/day administered orally, half in the morning and half in the evening. Participants titrated GWP42003-P to 10 mg/kg/day over 7 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day) period.</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>Participants received placebo (0 mg/mL CBD), volume matched to 1 of the 2 dose levels (10 or 20 mg/kg/day), administered orally, half in the morning and half in the evening. To maintain the blinded aspect of the study, participants titrated the placebo dose over 7 to 11 days according to the matched IMP group (7 or 11 days for the 10 or 20 mg/kg/day GWP42003-P groups, respectively) and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day of the matched dose) period.</description>
          </group>
        </group_list>
        <measure>
          <title>Number Of Participants With A ≥50% Reduction From Baseline In Drop Seizure Frequency During The Treatment Period</title>
          <description>Drop seizures were recorded by the participant or caregiver using an IVRS diary. Drop seizures included the subset of tonic-clonic, tonic, or atonic seizures that were reported as drop seizures in IVRS. Percentage change from baseline was calculated as per the primary outcome measure.</description>
          <population>ITT Analysis Set: Received at least 1 dose of IMP with at least 1 post-baseline efficacy endpoint measurement. Participants were analyzed according to the treatment group to which they were randomized.</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="76"/>
                <count group_id="O2" value="73"/>
                <count group_id="O3" value="76"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="30"/>
                    <measurement group_id="O2" value="26"/>
                    <measurement group_id="O3" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <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>0.0006</p_value>
            <p_value_desc>Calculated using a Cochran-Mantel-Haenszel (CMH) test stratified by age group (2-5, 6-11, 12-17 and 18-55 years)</p_value_desc>
            <method>Cochran-Mantel-Haenszel</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>3.85</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.75</ci_lower_limit>
            <ci_upper_limit>8.47</ci_upper_limit>
          </analysis>
          <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>0.0030</p_value>
            <p_value_desc>Calculated using a CMH test stratified by age group (2-5, 6-11, 12-17 and 18-55 years)</p_value_desc>
            <method>Cochran-Mantel-Haenszel</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>3.27</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.47</ci_lower_limit>
            <ci_upper_limit>7.26</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage Change From Baseline In Total Seizure Frequency During The Treatment Period</title>
        <description>Total seizures included the sum of all seizures (tonic-clonic, tonic, atonic, clonic, myoclonic, countable partial, other partial, and absence seizures) recorded by the participant or caregiver using an IVRS diary. Percentage change from baseline was calculated as per the primary outcome measure. Negative percentages show an improvement from baseline.</description>
        <time_frame>Baseline to EOT (Day 99) or ET</time_frame>
        <population>ITT Analysis Set: Received at least 1 dose of IMP with at least 1 post-baseline efficacy endpoint measurement. Participants were analyzed according to the treatment group to which they were randomized.</population>
        <group_list>
          <group group_id="O1">
            <title>GWP42003-P 20 mg/kg/Day Dose</title>
            <description>Participants received GWP42003-P 20 mg/kg/day administered orally, half in the morning and half in the evening. Participants titrated GWP42003-P to 20 mg/kg/day over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day) period.</description>
          </group>
          <group group_id="O2">
            <title>GWP42003-P 10 mg/kg/Day Dose</title>
            <description>Participants received GWP42003-P 10 mg/kg/day administered orally, half in the morning and half in the evening. Participants titrated GWP42003-P to 10 mg/kg/day over 7 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day) period.</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>Participants received placebo (0 mg/mL CBD), volume matched to 1 of the 2 dose levels (10 or 20 mg/kg/day), administered orally, half in the morning and half in the evening. To maintain the blinded aspect of the study, participants titrated the placebo dose over 7 to 11 days according to the matched IMP group (7 or 11 days for the 10 or 20 mg/kg/day GWP42003-P groups, respectively) and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day of the matched dose) period.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage Change From Baseline In Total Seizure Frequency During The Treatment Period</title>
          <description>Total seizures included the sum of all seizures (tonic-clonic, tonic, atonic, clonic, myoclonic, countable partial, other partial, and absence seizures) recorded by the participant or caregiver using an IVRS diary. Percentage change from baseline was calculated as per the primary outcome measure. Negative percentages show an improvement from baseline.</description>
          <population>ITT Analysis Set: Received at least 1 dose of IMP with at least 1 post-baseline efficacy endpoint measurement. Participants were analyzed according to the treatment group to which they were randomized.</population>
          <units>percentage change</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="76"/>
                <count group_id="O2" value="73"/>
                <count group_id="O3" value="76"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-38.40" lower_limit="-64.6" upper_limit="-0.7"/>
                    <measurement group_id="O2" value="-36.44" lower_limit="-64.5" upper_limit="-10.8"/>
                    <measurement group_id="O3" value="-18.47" lower_limit="-39.0" upper_limit="0.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <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>0.0091</p_value>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>-18.76</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-31.80</ci_lower_limit>
            <ci_upper_limit>-4.43</ci_upper_limit>
            <estimate_desc>Calculated using the Hodges-Lehmann approach</estimate_desc>
          </analysis>
          <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>0.0015</p_value>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>-19.47</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-30.37</ci_lower_limit>
            <ci_upper_limit>-7.47</ci_upper_limit>
            <estimate_desc>Calculated using the Hodges-Lehmann approach</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Subject/Caregiver Global Impression Of Change (S/CGIC) Assessment</title>
        <description>The S/CGIC was used to assess the participant's overall condition on a 7-point scale, using the markers &quot;very much improved, much improved, slightly improved, no change, slightly worse, much worse, or very much worse&quot; (1 = very much improved; 7 = very much worse). On Day 1 (prior to starting IMP), the caregiver was asked to write a brief description of the participant's overall condition as a memory aid for the S/CGIC questionnaire at subsequent visits. If both a CGIC and SGIC were completed then the CGIC was used; if only a CGIC was completed then the CGIC was used; if only a SGIC was completed then the SGIC was used. Last visit for endpoints assessed at clinic visits was defined as the last scheduled visit (not including the end of taper or safety follow-up visits) at which participant's last evaluation was performed.</description>
        <time_frame>Baseline to Last Visit (Day 99) or ET</time_frame>
        <population>ITT Analysis Set: Received at least 1 dose of IMP with at least 1 post-baseline efficacy endpoint measurement. Participants were analyzed according to the treatment group to which they were randomized.</population>
        <group_list>
          <group group_id="O1">
            <title>GWP42003-P 20 mg/kg/Day Dose</title>
            <description>Participants received GWP42003-P 20 mg/kg/day administered orally, half in the morning and half in the evening. Participants titrated GWP42003-P to 20 mg/kg/day over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day) period.</description>
          </group>
          <group group_id="O2">
            <title>GWP42003-P 10 mg/kg/Day Dose</title>
            <description>Participants received GWP42003-P 10 mg/kg/day administered orally, half in the morning and half in the evening. Participants titrated GWP42003-P to 10 mg/kg/day over 7 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day) period.</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>Participants received placebo (0 mg/mL CBD), volume matched to 1 of the 2 dose levels (10 or 20 mg/kg/day), administered orally, half in the morning and half in the evening. To maintain the blinded aspect of the study, participants titrated the placebo dose over 7 to 11 days according to the matched IMP group (7 or 11 days for the 10 or 20 mg/kg/day GWP42003-P groups, respectively) and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day of the matched dose) period.</description>
          </group>
        </group_list>
        <measure>
          <title>Subject/Caregiver Global Impression Of Change (S/CGIC) Assessment</title>
          <description>The S/CGIC was used to assess the participant's overall condition on a 7-point scale, using the markers &quot;very much improved, much improved, slightly improved, no change, slightly worse, much worse, or very much worse&quot; (1 = very much improved; 7 = very much worse). On Day 1 (prior to starting IMP), the caregiver was asked to write a brief description of the participant's overall condition as a memory aid for the S/CGIC questionnaire at subsequent visits. If both a CGIC and SGIC were completed then the CGIC was used; if only a CGIC was completed then the CGIC was used; if only a SGIC was completed then the SGIC was used. Last visit for endpoints assessed at clinic visits was defined as the last scheduled visit (not including the end of taper or safety follow-up visits) at which participant's last evaluation was performed.</description>
          <population>ITT Analysis Set: Received at least 1 dose of IMP with at least 1 post-baseline efficacy endpoint measurement. Participants were analyzed according to the treatment group to which they were randomized.</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="75"/>
                <count group_id="O2" value="73"/>
                <count group_id="O3" value="75"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Very Much Improved</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="9"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Much Improved</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15"/>
                    <measurement group_id="O2" value="14"/>
                    <measurement group_id="O3" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Slightly Improved</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22"/>
                    <measurement group_id="O2" value="25"/>
                    <measurement group_id="O3" value="24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>No Change</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25"/>
                    <measurement group_id="O2" value="21"/>
                    <measurement group_id="O3" value="35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Slightly Worse</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Much Worse</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Very Much Worse</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <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>0.0439</p_value>
            <method>Regression, Logistic</method>
            <method_desc>Ordinal logistic regression model with treatment group as a fixed factor</method_desc>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>1.83</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.02</ci_lower_limit>
            <ci_upper_limit>3.30</ci_upper_limit>
            <estimate_desc>Odds of participant recording a lower score (improvement) on a continuous scale</estimate_desc>
          </analysis>
          <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>0.0020</p_value>
            <method>Regression, Logistic</method>
            <method_desc>Ordinal logistic regression model with treatment group as a fixed factor</method_desc>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>2.57</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.41</ci_lower_limit>
            <ci_upper_limit>4.66</ci_upper_limit>
            <estimate_desc>Odds of participant recording a lower score (improvement) on a continuous scale</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Day 1 through Day 137 (Safety Follow-up)</time_frame>
      <desc>Safety Analysis Set: Received at least 1 dose of IMP; analyzed as per actual treatment received. Six participants who were assigned to the GWP42003-P 10 mg/kg/day dose received dosing schedules for GWP42003-P 20 mg/kg/day. For safety analyses, these participants were assigned to the GWP42003-P 20 mg/kg/day group.</desc>
      <group_list>
        <group group_id="E1">
          <title>GWP42003-P 20 mg/kg/Day Dose-Safety Analysis Set</title>
          <description>Participants received at least 1 dose of IMP; analyzed as per actual treatment received. Six participants who were assigned to the GWP42003-P 10 mg/kg/day dose received dosing schedules for GWP42003-P 20 mg/kg/day. For safety analyses, these participants were assigned to the GWP42003-P 20 mg/kg/day group.</description>
        </group>
        <group group_id="E2">
          <title>GWP42003-P 10 mg/kg/Day Dose-Safety Analysis Set</title>
          <description>Participants received at least 1 dose of IMP; analyzed as per actual treatment received. Six participants who were assigned to the GWP42003-P 10 mg/kg/day dose received dosing schedules for GWP42003-P 20 mg/kg/day. For safety analyses, these participants were assigned to the GWP42003-P 20 mg/kg/day group.</description>
        </group>
        <group group_id="E3">
          <title>Placebo-Safety Analysis Set</title>
          <description>Participants received at least 1 dose of IMP; analyzed as per actual treatment received.</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, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="82"/>
                <counts group_id="E2" subjects_affected="13" subjects_at_risk="67"/>
                <counts group_id="E3" subjects_affected="8" subjects_at_risk="76"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Lymphopenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="82"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="67"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="76"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="82"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="67"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Pneumatosis intestinalis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="82"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="67"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Pancreatitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="67"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Faecaloma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="67"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="76"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Device malfunction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="82"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="67"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="82"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="67"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="76"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Cholecystitis chronic</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="67"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="76"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="82"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="67"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Adenovirus infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="82"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="67"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Pneumonia mycoplasmal</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="82"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="67"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Respiratory syncytial virus infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="82"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="67"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="82"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="67"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Pneumonia bacterial</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="67"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Pneumonia respiratory syncytial viral</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="67"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Tracheobronchitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="67"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="76"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Delayed recovery from anaesthesia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="82"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="67"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="76"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="82"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="67"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="82"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="67"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Gamma-glutamyltransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="82"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="67"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Transaminases increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="67"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Investigation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="67"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="76"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="67"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="76"/>
              </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="4" subjects_at_risk="82"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="67"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Convulsion</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="82"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="67"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Lethargy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="82"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="67"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="82"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="67"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Sedation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="67"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="76"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Nephrolithiasis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="67"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="76"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="82"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="67"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="67"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Hypoventilation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="67"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Sleep apnoea syndrome</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="67"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="76"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="82"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="67"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="76"/>
              </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="63" subjects_at_risk="82"/>
                <counts group_id="E2" subjects_affected="36" subjects_at_risk="67"/>
                <counts group_id="E3" subjects_affected="40" subjects_at_risk="76"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="82"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="67"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="82"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="67"/>
                <counts group_id="E3" subjects_affected="9" subjects_at_risk="76"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="82"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="67"/>
                <counts group_id="E3" subjects_affected="12" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="82"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="67"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="76"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="82"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="67"/>
                <counts group_id="E3" subjects_affected="11" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="82"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="67"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="76"/>
              </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="21" subjects_at_risk="82"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="67"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="76"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" subjects_affected="25" subjects_at_risk="82"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="67"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Lethargy</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="82"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="67"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Convulsion</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="82"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="67"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="82"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="67"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="76"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Irritability</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="82"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="67"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="82"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="67"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="76"/>
              </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>
      <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/NCT02224560
org study id: GWEP1414
secondary id: 2014-002940-42
nct id: NCT02224560
lead sponsor: 
has dmc: Yes
The primary objective of this study was to evaluate the efficacy of GWP42003-P as adjunctive
      treatment in reducing the number of drop seizures when compared with placebo in participants
      with Lennox-Gastaut syndrome (LGS).
This study was a 1:1:1 randomized, double-blind, 14-week comparison of 2 dose levels (10
      milligram [mg] per kilogram [kg] per day [mg/kg/day] and 20 mg/kg/day) of GWP42003-P versus
      placebo. Participants who satisfied all inclusion and none of the exclusion criteria began a
      28-day baseline observation period. The treatment period consisted of a 2-week titration
      period followed by a 12-week maintenance period. 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). The 10 mg/kg/day dose was defined as 50% of the
      20 mg/kg/day dose. The first participant was not enrolled into this study until the DSMC had
      reviewed the safety data from Part A of study GWEP1332.

      Participants who satisfied all eligibility criteria were randomized at Day 1 to receive 10
      mg/kg/day GWP42003-P, 20 mg/kg/day GWP42003-P, or placebo at a 1:1:1 ratio. Participants in
      the placebo group were split into 2 equivalent cohorts; one half received 10 mg/kg/day dosing
      volumes and one half received 20 mg/kg/day dosing volumes. The 2 placebo cohorts were pooled
      for the analyses of efficacy. Participants titrated GWP42003-P to the 10 mg/kg/day or 20
      mg/kg/day (or equivalent volume of placebo) dose over 7 and 11 days, respectively, and
      remained at this dose for the 12-week maintenance period. Following the end of treatment (Day
      99), participants were invited to continue to receive GWP42003-P in an open-label extension
      (OLE) study under a separate protocol (GWEP1415; NCT02224573). All participants who did not
      immediately enter the OLE study tapered investigational medicinal product (IMP) (10% per day
      over 10 days). However, the taper period could be interrupted if the participant wished to
      enter the OLE study within a 7-day timeframe. Participants who down-titrated IMP returned for
      an end of taper period visit (Day 109). Participants who did not enter the OLE study or who
      withdrew prematurely had a safety follow-up visit 28 days later (Day 137).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Percentage Change From Baseline In Drop Seizure Frequency During The Treatment Period
time frame: Baseline to End of Treatment (EOT) (Day 99) or Early Termination (ET)
description: Drop seizures were recorded by the participant or caregiver using an interactive voice response system (IVRS) diary. Drop seizures were defined as the subset of tonic-clonic, tonic or atonic seizures that were reported as drop seizures in the IVRS. 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). Negative percentages show an improvement from baseline.
measure: Number Of Participants With A ≥50% Reduction From Baseline In Drop Seizure Frequency During The Treatment Period
time frame: Baseline to EOT (Day 99) or ET
description: Drop seizures were recorded by the participant or caregiver using an IVRS diary. Drop seizures included the subset of tonic-clonic, tonic, or atonic seizures that were reported as drop seizures in IVRS. Percentage change from baseline was calculated as per the primary outcome measure.
measure: Percentage Change From Baseline In Total Seizure Frequency During The Treatment Period
time frame: Baseline to EOT (Day 99) or ET
description: Total seizures included the sum of all seizures (tonic-clonic, tonic, atonic, clonic, myoclonic, countable partial, other partial, and absence seizures) recorded by the participant or caregiver using an IVRS diary. Percentage change from baseline was calculated as per the primary outcome measure. Negative percentages show an improvement from baseline.
measure: Subject/Caregiver Global Impression Of Change (S/CGIC) Assessment
time frame: Baseline to Last Visit (Day 99) or ET
description: The S/CGIC was used to assess the participant's overall condition on a 7-point scale, using the markers "very much improved, much improved, slightly improved, no change, slightly worse, much worse, or very much worse" (1 = very much improved; 7 = very much worse). On Day 1 (prior to starting IMP), the caregiver was asked to write a brief description of the participant's overall condition as a memory aid for the S/CGIC questionnaire at subsequent visits. If both a CGIC and SGIC were completed then the CGIC was used; if only a CGIC was completed then the CGIC was used; if only a SGIC was completed then the SGIC was used. Last visit for endpoints assessed at clinic visits was defined as the last scheduled visit (not including the end of taper or safety follow-up visits) at which participant's last evaluation was performed.
arm group label: GWP42003-P 20 mg/kg/day Dose
arm group type: Experimental
description: Participants received GWP42003-P 20 mg/kg/day administered orally, half in the morning and half in the evening. Participants titrated GWP42003-P to 20 mg/kg/day over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day) period.
arm group label: GWP42003-P 10 mg/kg/day Dose
arm group type: Experimental
description: Participants received GWP42003-P 10 mg/kg/day administered orally, half in the morning and half in the evening. Participants titrated GWP42003-P to 10 mg/kg/day over 7 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day) period.
arm group label: Placebo
arm group type: Placebo Comparator
description: Participants received placebo (0 mg/mL CBD) volume matched to 1 of the 2 dose levels (10 or 20 mg/kg/day) administered orally, half in the morning and half in the evening. To maintain the blinded aspect of the study, participants titrated the placebo dose over 7 to 11 days according to the matched IMP group (7 or 11 days for the 10 or 20 mg/kg/day GWP42003-P groups, respectively) and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day of the matched dose) period.
intervention type: Drug
intervention name: GWP42003-P
description: GWP42003-P was presented as an oral solution containing 100 mg/milliliter (mL) cannabidiol (CBD) in the excipients sesame oil and anhydrous ethanol (79 mg/mL) with added sweetener (0.5 mg/mL sucralose) and strawberry flavoring (0.2 mg/mL). Participants were randomly assigned to receive either 10 or 20 mg/kg/day.
arm group label: GWP42003-P 10 mg/kg/day Dose
arm group label: GWP42003-P 20 mg/kg/day Dose
other name: Cannabidiol
other name: Epidiolex
intervention type: Drug
intervention name: Placebo control
description: Placebo was presented as an oral solution containing 0 mg/mL CBD in the excipients sesame oil and anhydrous ethanol (79 mg/mL) with added sweetener (0.5 mg/mL sucralose) and strawberry flavoring (0.2 mg/mL).
arm group label: Placebo
other name: Placebo
criteria: 
gender: All
minimum age: 2 Years
maximum age: 55 Years
healthy volunteers: No
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country: France
country: Spain
country: United Kingdom
country: United States
citation: Devinsky O, Patel AD, Cross JH, Villanueva V, Wirrell EC, Privitera M, Greenwood SM, Roberts C, Checketts D, VanLandingham KE, Zuberi SM; GWPCARE3 Study Group. Effect of Cannabidiol on Drop Seizures in the Lennox-Gastaut Syndrome. N Engl J Med. 2018 May 17;378(20):1888-1897. doi: 10.1056/NEJMoa1714631.
PMID: 29768152
responsible party type: Sponsor
mesh term: Seizures
mesh term: Lennox Gastaut Syndrome
mesh term: Syndrome
mesh term: Cannabidiol
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 