<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/NCT02224690</url>
  </required_header>
  <id_info>
    <org_study_id>GWEP1423</org_study_id>
    <secondary_id>2014-002941-23</secondary_id>
    <nct_id>NCT02224690</nct_id>
  </id_info>
  <brief_title>A 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</brief_title>
  <acronym>GWPCARE4</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>
      To evaluate the efficacy of GWP42003-P as adjunctive treatment in reducing the number of drop&#xD;
      seizures when compared with placebo, in participants with Lennox-Gastaut Syndrome (LGS).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study was a 1:1 randomized, double-blind, 14-week comparison of 20 milligram [mg] per&#xD;
      kilogram [kg] per day [mg/kg/day] of GWP42003-P versus placebo. The treatment period&#xD;
      consisted of a 2-week titration period followed by a 12-week maintenance period. The study&#xD;
      determined the efficacy, safety and tolerability of GWP42003-P compared with placebo. The&#xD;
      dose was recommended by the Data Safety Monitoring Committee (DSMC) after assessment of&#xD;
      safety and pharmacokinetic data from Part A of study GWEP1332. The first participants&#xD;
      enrolled into this study after the DSMC reviewed the safety data from Part A of study&#xD;
      GWEP1332. Following study completion, all participants were invited to continue to receive&#xD;
      GWP42003-P in an open label extension (OLE) study (under a separate protocol).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 28, 2015</start_date>
  <completion_date type="Actual">March 18, 2016</completion_date>
  <primary_completion_date type="Actual">March 18, 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) * 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) *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 Assessment (S/CGIC)</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>2</number_of_arms>
  <enrollment type="Actual">171</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>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants received placebo (0 mg/mL CBD), volume matched to the 20 mg/kg/day dose, 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 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>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>GWP42003-P 20 mg/kg/day Dose</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).</description>
    <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</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>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria:&#xD;
&#xD;
          -  Participant must have been male or female aged between 2 and 55 years (inclusive).&#xD;
&#xD;
          -  Participant must have had a documented history of Lennox-Gastaut syndrome. This&#xD;
             included written documentation of having met electroencephalogram (EEG) diagnostic&#xD;
             criteria during the participant's history and evidence of at least 1 type of&#xD;
             generalized seizure, including drop seizures (atonic, tonic, tonic-clonic or&#xD;
             myoclonic) for at least 6 months.&#xD;
&#xD;
          -  Participants had a history of slow (&lt;3.0 Hertz) spike-and-wave pattern in an EEG prior&#xD;
             to the enrollment into the baseline period.&#xD;
&#xD;
          -  Participants were refractory; that is having documented failures on more than one&#xD;
             antiepileptic drug (AED).&#xD;
&#xD;
          -  Participant must have been taking 1 or more AEDs at a dose which has been stable for&#xD;
             at least 4 weeks prior to screening.&#xD;
&#xD;
          -  All medications or interventions for epilepsy (including ketogenic diet and vagus&#xD;
             nerve stimulation [VNS]) must have been stable for 4 weeks prior to screening and&#xD;
             participant is willing to maintain a stable regimen throughout the study. The&#xD;
             ketogenic diet and VNS treatments are not accounted as an AED.&#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 was currently using or has 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 any known or suspected hypersensitivity to cannabinoids or any of the&#xD;
             excipients of the Investigational Medicinal Product (IMP), such as sesame oil.&#xD;
&#xD;
          -  Participant had been part of a clinical trial involving another IMP in the previous 6&#xD;
             months.&#xD;
&#xD;
          -  Participant had significantly impaired hepatic function at screening or randomization&#xD;
             (Alanine aminotransferase [ALT] &gt;5 x upper limit of normal [ULN] or total bilirubin&#xD;
             [TBL] &gt;2 x ULN) OR the ALT or Aspartate aminotransferase (AST) &gt;3 x ULN and (TBL &gt;2 x&#xD;
             ULN or international normalized ratio &gt;1.5). This criterion can only be confirmed once&#xD;
             the laboratory results are available; Participants randomized into the study who are&#xD;
             later found not to meet this criterion should be withdrawn from the 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 taking more than 4 concurrent AEDs.&#xD;
&#xD;
          -  Participant was taking corticotropins in the 6 months prior to screening.&#xD;
&#xD;
          -  Participant was taking long-term systemic steroids (excluding inhaled medication for&#xD;
             asthma treatment) or any other daily medication known to exacerbate epilepsy. An&#xD;
             exception was made of prophylactic medication, for example, idiopathic nephrotic&#xD;
             syndrome or asthma.&#xD;
&#xD;
          -  Participant was taking felbamate, and they had been taking it for less than 1 year&#xD;
             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>Tampa</city>
        <state>Florida</state>
        <zip>33606</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30328</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Ames</city>
        <state>Iowa</state>
        <zip>50010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Iowa City</city>
        <state>Iowa</state>
        <zip>52242</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Lexington</city>
        <state>Kentucky</state>
        <zip>40536</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Saint Paul</city>
        <state>Minnesota</state>
        <zip>55102</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63131</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Lebanon</city>
        <state>New Hampshire</state>
        <zip>03756</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Bronx</city>
        <state>New York</state>
        <zip>10467</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Rochester</city>
        <state>New York</state>
        <zip>14642</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104-4399</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75251</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>81143</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Winchester</city>
        <state>Virginia</state>
        <zip>22601</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Denekamp</city>
        <state>BV Zwolle</state>
        <zip>8025</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Bydgoszcz</city>
        <zip>85-080</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Gdańsk</city>
        <zip>80-952</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Kraków</city>
        <zip>30-349</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Lublin</city>
        <zip>20-093</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Lublin</city>
        <zip>20-718</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Poznań</city>
        <zip>60-355</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
    <country>Poland</country>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Thiele EA, Marsh ED, French JA, Mazurkiewicz-Beldzinska M, Benbadis SR, Joshi C, Lyons PD, Taylor A, Roberts C, Sommerville K; GWPCARE4 Study Group. Cannabidiol in patients with seizures associated with Lennox-Gastaut syndrome (GWPCARE4): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2018 Mar 17;391(10125):1085-1096. doi: 10.1016/S0140-6736(18)30136-3. Epub 2018 Jan 26.</citation>
    <PMID>29395273</PMID>
  </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>February 22, 2017</disposition_first_submitted>
  <disposition_first_submitted_qc>February 22, 2017</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">February 23, 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 level of 20 milligram (mg) per kilogram (kg) per day (mg/kg/day) was recommended by the GWEP1332 Part A (NCT02091206) Data Safety Monitoring Committee after assessment of safety and pharmacokinetic data. The investigational medicinal product (IMP) was given daily in 2 divided doses (the preferred dosing regimen for antiepileptic drugs).</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>Placebo</title>
          <description>Participants received placebo (0 mg/milliliter [mL] cannabidiol [CBD]), volume matched to the 20 mg/kg/day dose, 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 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_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="86"/>
                <participants group_id="P2" count="85"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Safety Analysis Set</title>
              <participants_list>
                <participants group_id="P1" count="86"/>
                <participants group_id="P2" count="85"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Intent to Treat (ITT) Analysis Set</title>
              <participants_list>
                <participants group_id="P1" count="86"/>
                <participants group_id="P2" count="85"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="72"/>
                <participants group_id="P2" count="84"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Met Withdrawal Criteria</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Use of G-tube</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Did not meet eligibility criteria</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>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="B2">
          <title>Placebo</title>
          <description>Participants received placebo (0 mg/mL CBD), volume matched to the 20 mg/kg/day dose, 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 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="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="86"/>
            <count group_id="B2" value="85"/>
            <count group_id="B3" value="171"/>
          </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="15.478" spread="8.685"/>
                    <measurement group_id="B2" value="15.284" spread="9.7945"/>
                    <measurement group_id="B3" value="15.381" spread="9.2264"/>
                  </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="41"/>
                    <measurement group_id="B2" value="42"/>
                    <measurement group_id="B3" value="83"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="45"/>
                    <measurement group_id="B2" value="43"/>
                    <measurement group_id="B3" value="88"/>
                  </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) * 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) *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: All randomized participants who received at least 1 dose of IMP and had 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>Placebo</title>
            <description>Participants received placebo (0 mg/mL CBD), volume matched to the 20 mg/kg/day dose, 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 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_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) * 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) *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: All randomized participants who received at least 1 dose of IMP and had 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="86"/>
                <count group_id="O2" value="85"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-43.90" lower_limit="-69.62" upper_limit="1.93"/>
                    <measurement group_id="O2" value="-21.80" lower_limit="-45.72" upper_limit="1.74"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0135</p_value>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>-17.21</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-30.32</ci_lower_limit>
            <ci_upper_limit>-4.09</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: All randomized participants who received at least 1 dose of IMP and had 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>Placebo</title>
            <description>Participants received placebo (0 mg/mL CBD), volume matched to the 20 mg/kg/day dose, 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 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_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: All randomized participants who received at least 1 dose of IMP and had 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="86"/>
                <count group_id="O2" value="85"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="38"/>
                    <measurement group_id="O2" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0043</p_value>
            <method>Cochran-Mantel-Haenszel</method>
            <method_desc>Calculated using a Cochran-Mantel-Haenszel test stratified by age group (2-5, 6-11, 12-17 and 18-55 years)</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>1.33</ci_lower_limit>
            <ci_upper_limit>4.97</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: All randomized participants who received at least 1 dose of IMP and had 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>Placebo</title>
            <description>Participants received placebo (0 mg/mL CBD), volume matched to the 20 mg/kg/day dose, 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 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_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: All randomized participants who received at least 1 dose of IMP and had 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="86"/>
                <count group_id="O2" value="85"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-41.24" lower_limit="-62.85" upper_limit="-13.00"/>
                    <measurement group_id="O2" value="-13.70" lower_limit="-45.00" upper_limit="7.27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0005</p_value>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-21.13</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-33.26</ci_lower_limit>
            <ci_upper_limit>-9.37</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 Assessment (S/CGIC)</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: All randomized participants who received at least 1 dose of IMP and had 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>Placebo</title>
            <description>Participants received placebo (0 mg/mL CBD), volume matched to the 20 mg/kg/day dose, 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 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_list>
        <measure>
          <title>Subject/Caregiver Global Impression Of Change Assessment (S/CGIC)</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: All randomized participants who received at least 1 dose of IMP and had 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="84"/>
                <count group_id="O2" value="85"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Very Much Improved</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15"/>
                    <measurement group_id="O2" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Much Improved</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14"/>
                    <measurement group_id="O2" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Slightly Improved</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20"/>
                    <measurement group_id="O2" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>No Change</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="27"/>
                    <measurement group_id="O2" value="43"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Slightly Worse</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="9"/>
                  </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="2"/>
                  </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="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0012</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>2.54</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.45</ci_lower_limit>
            <ci_upper_limit>4.47</ci_upper_limit>
            <estimate_desc>Odds of participants 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: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.</desc>
      <group_list>
        <group group_id="E1">
          <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="E2">
          <title>Placebo</title>
          <description>Participants received placebo (0 mg/mL CBD), volume matched to the 20 mg/kg/day dose, 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 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_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="20" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="85"/>
              </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="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="85"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="85"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute hepatic failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="85"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Perirectal abscess</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Pilonidal cyst</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Pneumonia adenoviral</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Viral infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="85"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Drug level increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Gamma-glutamyltransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Liver function test abnormal</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Oxygen saturation decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Transaminases increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="85"/>
              </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="86"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="85"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Convulsion</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Generalised tonic-clonic seizure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Lethargy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Seizure cluster</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Status epilepticus</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="85"/>
              </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="1" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="85"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Acute respiratory distress</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Acute respiratory failure</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Bronchial secretion retention</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Hypercapnia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Pneumonia aspiration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Pneumothorax</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Respiratory distress</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Sleep apnoea syndrome</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="85"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Deep vein thrombosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="85"/>
              </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="53" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="43" subjects_at_risk="85"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="85"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="85"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="85"/>
              </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="11" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="85"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Sedation</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Convulsion</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="85"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="85"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="85"/>
              </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 Enquires</name_or_title>
      <organization>GW Research Ltd.</organization>
      <email>medinfo.USA@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/NCT02224690
org study id: GWEP1423
secondary id: 2014-002941-23
nct id: NCT02224690
lead sponsor: 
has dmc: Yes
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 randomized, double-blind, 14-week comparison of 20 milligram [mg] per
      kilogram [kg] per day [mg/kg/day] of GWP42003-P versus placebo. The treatment period
      consisted of a 2-week titration period followed by a 12-week maintenance period. The study
      determined the efficacy, safety and tolerability of GWP42003-P compared with placebo. The
      dose was recommended by the Data Safety Monitoring Committee (DSMC) after assessment of
      safety and pharmacokinetic data from Part A of study GWEP1332. The first participants
      enrolled into this study after the DSMC reviewed the safety data from Part A of study
      GWEP1332. Following study completion, all participants were invited to continue to receive
      GWP42003-P in an open label extension (OLE) study (under a separate protocol).
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) * 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) *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 Assessment (S/CGIC)
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: Placebo
arm group type: Placebo Comparator
description: Participants received placebo (0 mg/mL CBD), volume matched to the 20 mg/kg/day dose, 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 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.
intervention type: Drug
intervention name: GWP42003-P 20 mg/kg/day Dose
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).
arm group label: GWP42003-P 20 mg/kg/day Dose
other name: Cannabidiol
other name: Epidiolex
intervention type: Drug
intervention name: Placebo
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
criteria: 
gender: All
minimum age: 2 Years
maximum age: 55 Years
healthy volunteers: No
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country: Netherlands
country: Poland
country: United States
citation: Thiele EA, Marsh ED, French JA, Mazurkiewicz-Beldzinska M, Benbadis SR, Joshi C, Lyons PD, Taylor A, Roberts C, Sommerville K; GWPCARE4 Study Group. Cannabidiol in patients with seizures associated with Lennox-Gastaut syndrome (GWPCARE4): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2018 Mar 17;391(10125):1085-1096. doi: 10.1016/S0140-6736(18)30136-3. Epub 2018 Jan 26.
PMID: 29395273
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: 