<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/NCT03303079</url>
  </required_header>
  <id_info>
    <org_study_id>406-102-00001</org_study_id>
    <secondary_id>JapicCTI-173723</secondary_id>
    <nct_id>NCT03303079</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety of Subcutaneous Administration of TEV-48125 for the Preventive Treatment of Chronic Migraine</brief_title>
  <official_title>A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Trial Evaluating the Efficacy and Safety of Subcutaneous Administration of TEV-48125 for the Preventive Treatment of Chronic Migraine</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Otsuka Pharmaceutical Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Otsuka Pharmaceutical Co., Ltd.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      To evaluate the efficacy and safety of subcutaneous (SC) administration of TEV-48125 [monthly&#xD;
      TEV-48125 225 mg (loading dose only: 675 mg) and TEV-48125 675 mg once over a period of 3&#xD;
      months] compared with placebo for preventive treatment in Chronic Migraine patients&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 19, 2017</start_date>
  <completion_date type="Actual">November 30, 2019</completion_date>
  <primary_completion_date type="Actual">November 30, 2019</primary_completion_date>
  <phase>Phase 2/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>Mean Change From Baseline in the Monthly (28 Day) Average Number of Headache Days of at Least Moderate Severity During the 12-week Period After the First Dose of Investigational Medicinal Product (IMP)</measure>
    <time_frame>Baseline, 12 weeks</time_frame>
    <description>Headache-related efficacy endpoints were derived from headache variables collected using an eDiary. On each day, subjects entered headache data in the electronic headache diary for the previous 24-hour period. Subjects who had experienced headache on the previous day answered questions about the headache (ie, occurrence of headache, duration of headache, maximum severity of headache, presence/absence of associated symptoms, and use of acute headache medications). Overall headache duration was recorded numerically, in hours, as well as number of hours with headache of at least moderate severity. If headache was reported, then headache severity was subjectively rated by the subject as mild, moderate, or severe.&#xD;
Subjects also recorded the presence or absence of photophobia, phonophobia, nausea, or vomiting, and the status of use of any acute headache medications.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mean Change From Baseline in the Monthly Average Number of Migraine Days During the 12-week Period After the First Dose of IMP</measure>
    <time_frame>Baseline, 12 weeks</time_frame>
    <description>Headache-related efficacy endpoints were derived from headache variables collected using an eDiary. On each day, subjects entered headache data in the electronic headache diary for the previous 24-hour period. Subjects who had experienced headache on the previous day answered questions about the headache (ie, occurrence of headache, duration of headache, maximum severity of headache, presence/absence of associated symptoms, and use of acute headache medications). Overall headache duration was recorded numerically, in hours, as well as number of hours with headache of at least moderate severity. If headache was reported, then headache severity was subjectively rated by the subject as mild, moderate, or severe.&#xD;
Subjects also recorded the presence or absence of photophobia, phonophobia, nausea, or vomiting, and the status of use of any acute headache medications.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of Subjects Reaching at Least 50% Reduction in the Monthly Average Number of Headache Days of at Least Moderate Severity During the 12-week Period After the First Dose of IMP</measure>
    <time_frame>12 weeks</time_frame>
    <description>Headache-related efficacy endpoints were derived from headache variables collected using an eDiary. On each day, subjects entered headache data in the electronic headache diary for the previous 24-hour period. Subjects who had experienced headache on the previous day answered questions about the headache (ie, occurrence of headache, duration of headache, maximum severity of headache, presence/absence of associated symptoms, and use of acute headache medications). Overall headache duration was recorded numerically, in hours, as well as number of hours with headache of at least moderate severity. If headache was reported, then headache severity was subjectively rated by the subject as mild, moderate, or severe.&#xD;
Subjects also recorded the presence or absence of photophobia, phonophobia, nausea, or vomiting, and the status of use of any acute headache medications.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Change From Baseline in the Monthly Average Number of Days With Use of Any Acute Headache Medications During the 12-week Period After the First Dose of IMP</measure>
    <time_frame>Baseline, 12 weeks</time_frame>
    <description>Headache-related efficacy endpoints were derived from headache variables collected using an eDiary. On each day, subjects entered headache data in the electronic headache diary for the previous 24-hour period. Subjects who had experienced headache on the previous day answered questions about the headache (ie, occurrence of headache, duration of headache, maximum severity of headache, presence/absence of associated symptoms, and use of acute headache medications).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Change From Baseline in the Monthly Average Number of Headache Days of at Least Moderate Severity During the 12-week Period After the First Dose of IMP in Subjects Not Receiving Concomitant Preventive Migraine Medications</measure>
    <time_frame>Baseline, 12 weeks</time_frame>
    <description>Headache-related efficacy endpoints were derived from headache variables collected using an eDiary. On each day, subjects entered headache data in the electronic headache diary for the previous 24-hour period. Subjects who had experienced headache on the previous day answered questions about the headache (ie, occurrence of headache, duration of headache, maximum severity of headache, presence/absence of associated symptoms, and use of acute headache medications). Overall headache duration was recorded numerically, in hours, as well as number of hours with headache of at least moderate severity. If headache was reported, then headache severity was subjectively rated by the subject as mild, moderate, or severe.&#xD;
Subjects also recorded the presence or absence of photophobia, phonophobia, nausea, or vomiting, and the status of use of any acute headache medications.&quot;</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Change From Baseline in Disability Score, as Measured by 6-Item Headache Impact Test (HIT-6) at 4 Weeks After the Final (Third) Dose of IMP</measure>
    <time_frame>Baseline, 4 weeks</time_frame>
    <description>Subjects assessed the impact of headache on social functioning, role functioning, vitality, cognitive functioning, and psychological distress, using the HIT-6. The HIT-6 total score will be obtained from summation of the 6 question points.Each question is answered on the scale ranging with the following response options: 6 points (never), 8 points (rarely), 10 points (sometimes), 11 points (very often), and 13 points (always).</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">571</enrollment>
  <condition>Migraine</condition>
  <arm_group>
    <arm_group_label>TEV-48125 (675/225/225 mg) group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>TEV-48125 will be subcutaneously administered once monthly for 3 months (675/225/225 mg).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>TEV-48125 (675 mg/placebo/placebo) group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>TEV-48125 or placebo will be subcutaneously administered once monthly for 3 months (675 mg/ placebo/placebo).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo will be subcutaneously administered once monthly for 3 months (placebo/placebo/placebo).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TEV-48125</intervention_name>
    <description>TEV-48125 will be subcutaneously administered once monthly for 3 months.</description>
    <arm_group_label>TEV-48125 (675/225/225 mg) group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TEV-48125 or placebo</intervention_name>
    <description>TEV-48125 or placebo will be subcutaneously administered once monthly for 3 months.</description>
    <arm_group_label>TEV-48125 (675 mg/placebo/placebo) group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo will be subcutaneously administered once monthly for 3 months.</description>
    <arm_group_label>Placebo group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patient has a history of migraine (according to The International Classification of&#xD;
             Headache Disorders, third edition [beta version] criteria) or clinical judgment&#xD;
             suggests a migraine diagnosis&#xD;
&#xD;
          -  Patient fulfills the criteria for Chronic migraine in baseline information collected&#xD;
             during the 28 day screening period&#xD;
&#xD;
          -  Not using preventive migraine medications for migraine or other medical conditions or&#xD;
             using no more than 1 preventive migraine medication for migraine or other medical&#xD;
             conditions if the dose and regimen have been stable for at least 2 months prior to&#xD;
             giving informed consent.&#xD;
&#xD;
          -  Patient demonstrates compliance with the electronic headache diary during the&#xD;
             screening period by entry of headache data on a minimum of 24 of 28 days and the&#xD;
             entered data is judged appropriate by the investigator.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients who have previously failed (lack of efficacy) 2 or more of the clusters of&#xD;
             the medications for treatment of migraine after use for at least 3 months at accepted&#xD;
             migraine therapeutic doses&#xD;
&#xD;
          -  Patient suffers from unremitting headaches, defined as having headaches for more than&#xD;
             80% of the time that he/she is awake, and less than 4 days without headache per month.&#xD;
             Daily headache is acceptable if the patient has headaches 80% or less of the time they&#xD;
             are awake on most days.&#xD;
&#xD;
          -  Hematological, cardiac, renal, endocrine, pulmonary, gastrointestinal, genitourinary,&#xD;
             neurologic, hepatic, or ocular disease considered clinically significant in the&#xD;
             judgment of the investigator&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Takehisa Matsumaru</last_name>
    <role>Study Director</role>
    <affiliation>Otsuka Pharmaceutical Co., Ltd.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Saitama Medical University Hospital</name>
      <address>
        <city>Iruma</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Japan</country>
  </location_countries>
  <verification_date>May 2021</verification_date>
  <study_first_submitted>October 2, 2017</study_first_submitted>
  <study_first_submitted_qc>October 2, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 5, 2017</study_first_posted>
  <results_first_submitted>May 20, 2021</results_first_submitted>
  <results_first_submitted_qc>May 20, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">June 15, 2021</results_first_posted>
  <last_update_submitted>May 20, 2021</last_update_submitted>
  <last_update_submitted_qc>May 20, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">June 15, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Migraine Disorders</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Antibodies, Monoclonal</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>July 8, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/79/NCT03303079/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>December 12, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/79/NCT03303079/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>TEV-48125 (675/225/225 mg) Group</title>
          <description>TEV-48125 will be subcutaneously administered once monthly for 3 months (675/225/225 mg).</description>
        </group>
        <group group_id="P2">
          <title>TEV-48125 (675 mg/Placebo/Placebo) Group</title>
          <description>TEV-48125 or placebo will be subcutaneously administered once monthly for 3 months (675 mg/ placebo/placebo).</description>
        </group>
        <group group_id="P3">
          <title>Placebo Group</title>
          <description>Placebo will be subcutaneously administered once monthly for 3 months (placebo/placebo/placebo).</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="189"/>
                <participants group_id="P2" count="191"/>
                <participants group_id="P3" count="191"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="182"/>
                <participants group_id="P2" count="180"/>
                <participants group_id="P3" count="179"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="11"/>
                <participants group_id="P3" count="12"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="4"/>
                <participants group_id="P3" count="7"/>
              </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="4"/>
                <participants group_id="P3" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other than specified</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>TEV-48125 (675/225/225 mg) Group</title>
          <description>TEV-48125 will be subcutaneously administered once monthly for 3 months (675/225/225 mg).</description>
        </group>
        <group group_id="B2">
          <title>TEV-48125 (675 mg/Placebo/Placebo) Group</title>
          <description>TEV-48125 or placebo will be subcutaneously administered once monthly for 3 months (675 mg/ placebo/placebo).</description>
        </group>
        <group group_id="B3">
          <title>Placebo Group</title>
          <description>Placebo will be subcutaneously administered once monthly for 3 months (placebo/placebo/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="189"/>
            <count group_id="B2" value="191"/>
            <count group_id="B3" value="191"/>
            <count group_id="B4" value="571"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="187"/>
                    <measurement group_id="B2" value="184"/>
                    <measurement group_id="B3" value="190"/>
                    <measurement group_id="B4" value="561"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <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="42.7" spread="10.2"/>
                    <measurement group_id="B2" value="43.5" spread="10.2"/>
                    <measurement group_id="B3" value="42.1" spread="10.2"/>
                    <measurement group_id="B4" value="42.8" spread="10.2"/>
                  </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="163"/>
                    <measurement group_id="B2" value="165"/>
                    <measurement group_id="B3" value="163"/>
                    <measurement group_id="B4" value="491"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="26"/>
                    <measurement group_id="B2" value="26"/>
                    <measurement group_id="B3" value="28"/>
                    <measurement group_id="B4" value="80"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Asian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="189"/>
                    <measurement group_id="B2" value="191"/>
                    <measurement group_id="B3" value="191"/>
                    <measurement group_id="B4" value="571"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Japan</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="159"/>
                    <measurement group_id="B2" value="159"/>
                    <measurement group_id="B3" value="161"/>
                    <measurement group_id="B4" value="479"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>South Korea</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="30"/>
                    <measurement group_id="B2" value="32"/>
                    <measurement group_id="B3" value="30"/>
                    <measurement group_id="B4" value="92"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Mean Change From Baseline in the Monthly (28 Day) Average Number of Headache Days of at Least Moderate Severity During the 12-week Period After the First Dose of Investigational Medicinal Product (IMP)</title>
        <description>Headache-related efficacy endpoints were derived from headache variables collected using an eDiary. On each day, subjects entered headache data in the electronic headache diary for the previous 24-hour period. Subjects who had experienced headache on the previous day answered questions about the headache (ie, occurrence of headache, duration of headache, maximum severity of headache, presence/absence of associated symptoms, and use of acute headache medications). Overall headache duration was recorded numerically, in hours, as well as number of hours with headache of at least moderate severity. If headache was reported, then headache severity was subjectively rated by the subject as mild, moderate, or severe.&#xD;
Subjects also recorded the presence or absence of photophobia, phonophobia, nausea, or vomiting, and the status of use of any acute headache medications.</description>
        <time_frame>Baseline, 12 weeks</time_frame>
        <population>Full Analysis set (FAS): Subjects who received the IMP at least once and had baseline and Week 12 data on monthly average number of headache days of at least moderate severity</population>
        <group_list>
          <group group_id="O1">
            <title>TEV-48125 (675/225/225 mg) Group</title>
            <description>TEV-48125 will be subcutaneously administered once monthly for 3 months (675/225/225 mg).</description>
          </group>
          <group group_id="O2">
            <title>TEV-48125 (675 mg/Placebo/Placebo) Group</title>
            <description>TEV-48125 or placebo will be subcutaneously administered once monthly for 3 months (675 mg/ placebo/placebo).</description>
          </group>
          <group group_id="O3">
            <title>Placebo Group</title>
            <description>Placebo will be subcutaneously administered once monthly for 3 months (placebo/placebo/placebo).</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change From Baseline in the Monthly (28 Day) Average Number of Headache Days of at Least Moderate Severity During the 12-week Period After the First Dose of Investigational Medicinal Product (IMP)</title>
          <description>Headache-related efficacy endpoints were derived from headache variables collected using an eDiary. On each day, subjects entered headache data in the electronic headache diary for the previous 24-hour period. Subjects who had experienced headache on the previous day answered questions about the headache (ie, occurrence of headache, duration of headache, maximum severity of headache, presence/absence of associated symptoms, and use of acute headache medications). Overall headache duration was recorded numerically, in hours, as well as number of hours with headache of at least moderate severity. If headache was reported, then headache severity was subjectively rated by the subject as mild, moderate, or severe.&#xD;
Subjects also recorded the presence or absence of photophobia, phonophobia, nausea, or vomiting, and the status of use of any acute headache medications.</description>
          <population>Full Analysis set (FAS): Subjects who received the IMP at least once and had baseline and Week 12 data on monthly average number of headache days of at least moderate severity</population>
          <units>days/month</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="187"/>
                <count group_id="O2" value="189"/>
                <count group_id="O3" value="190"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.12" spread="0.43"/>
                    <measurement group_id="O2" value="-4.14" spread="0.43"/>
                    <measurement group_id="O3" value="-2.45" spread="0.43"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change From Baseline in the Monthly Average Number of Migraine Days During the 12-week Period After the First Dose of IMP</title>
        <description>Headache-related efficacy endpoints were derived from headache variables collected using an eDiary. On each day, subjects entered headache data in the electronic headache diary for the previous 24-hour period. Subjects who had experienced headache on the previous day answered questions about the headache (ie, occurrence of headache, duration of headache, maximum severity of headache, presence/absence of associated symptoms, and use of acute headache medications). Overall headache duration was recorded numerically, in hours, as well as number of hours with headache of at least moderate severity. If headache was reported, then headache severity was subjectively rated by the subject as mild, moderate, or severe.&#xD;
Subjects also recorded the presence or absence of photophobia, phonophobia, nausea, or vomiting, and the status of use of any acute headache medications.</description>
        <time_frame>Baseline, 12 weeks</time_frame>
        <population>Full Analysis set (FAS): Subjects who received the IMP at least once and had baseline and Week 12 data on monthly average number of headache days of at least moderate severity</population>
        <group_list>
          <group group_id="O1">
            <title>TEV-48125 (675/225/225 mg) Group</title>
            <description>TEV-48125 will be subcutaneously administered once monthly for 3 months (675/225/225 mg).</description>
          </group>
          <group group_id="O2">
            <title>TEV-48125 (675 mg/Placebo/Placebo) Group</title>
            <description>TEV-48125 or placebo will be subcutaneously administered once monthly for 3 months (675 mg/ placebo/placebo).</description>
          </group>
          <group group_id="O3">
            <title>Placebo Group</title>
            <description>Placebo will be subcutaneously administered once monthly for 3 months (placebo/placebo/placebo).</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change From Baseline in the Monthly Average Number of Migraine Days During the 12-week Period After the First Dose of IMP</title>
          <description>Headache-related efficacy endpoints were derived from headache variables collected using an eDiary. On each day, subjects entered headache data in the electronic headache diary for the previous 24-hour period. Subjects who had experienced headache on the previous day answered questions about the headache (ie, occurrence of headache, duration of headache, maximum severity of headache, presence/absence of associated symptoms, and use of acute headache medications). Overall headache duration was recorded numerically, in hours, as well as number of hours with headache of at least moderate severity. If headache was reported, then headache severity was subjectively rated by the subject as mild, moderate, or severe.&#xD;
Subjects also recorded the presence or absence of photophobia, phonophobia, nausea, or vomiting, and the status of use of any acute headache medications.</description>
          <population>Full Analysis set (FAS): Subjects who received the IMP at least once and had baseline and Week 12 data on monthly average number of headache days of at least moderate severity</population>
          <units>days/month</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="187"/>
                <count group_id="O2" value="189"/>
                <count group_id="O3" value="190"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.90" spread="0.50"/>
                    <measurement group_id="O2" value="-4.07" spread="0.49"/>
                    <measurement group_id="O3" value="-2.79" spread="0.49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Proportion of Subjects Reaching at Least 50% Reduction in the Monthly Average Number of Headache Days of at Least Moderate Severity During the 12-week Period After the First Dose of IMP</title>
        <description>Headache-related efficacy endpoints were derived from headache variables collected using an eDiary. On each day, subjects entered headache data in the electronic headache diary for the previous 24-hour period. Subjects who had experienced headache on the previous day answered questions about the headache (ie, occurrence of headache, duration of headache, maximum severity of headache, presence/absence of associated symptoms, and use of acute headache medications). Overall headache duration was recorded numerically, in hours, as well as number of hours with headache of at least moderate severity. If headache was reported, then headache severity was subjectively rated by the subject as mild, moderate, or severe.&#xD;
Subjects also recorded the presence or absence of photophobia, phonophobia, nausea, or vomiting, and the status of use of any acute headache medications.</description>
        <time_frame>12 weeks</time_frame>
        <population>Full Analysis set (FAS): Subjects who received the IMP at least once and had baseline and Week 12 data on monthly average number of headache days of at least moderate severity &quot;Overall Number of Participants Analyzed&quot; = the number of subjects meeting responder criteria</population>
        <group_list>
          <group group_id="O1">
            <title>TEV-48125 (675/225/225 mg) Group</title>
            <description>TEV-48125 will be subcutaneously administered once monthly for 3 months (675/225/225 mg).</description>
          </group>
          <group group_id="O2">
            <title>TEV-48125 (675 mg/Placebo/Placebo) Group</title>
            <description>TEV-48125 or placebo will be subcutaneously administered once monthly for 3 months (675 mg/ placebo/placebo).</description>
          </group>
          <group group_id="O3">
            <title>Placebo Group</title>
            <description>Placebo will be subcutaneously administered once monthly for 3 months (placebo/placebo/placebo).</description>
          </group>
        </group_list>
        <measure>
          <title>Proportion of Subjects Reaching at Least 50% Reduction in the Monthly Average Number of Headache Days of at Least Moderate Severity During the 12-week Period After the First Dose of IMP</title>
          <description>Headache-related efficacy endpoints were derived from headache variables collected using an eDiary. On each day, subjects entered headache data in the electronic headache diary for the previous 24-hour period. Subjects who had experienced headache on the previous day answered questions about the headache (ie, occurrence of headache, duration of headache, maximum severity of headache, presence/absence of associated symptoms, and use of acute headache medications). Overall headache duration was recorded numerically, in hours, as well as number of hours with headache of at least moderate severity. If headache was reported, then headache severity was subjectively rated by the subject as mild, moderate, or severe.&#xD;
Subjects also recorded the presence or absence of photophobia, phonophobia, nausea, or vomiting, and the status of use of any acute headache medications.</description>
          <population>Full Analysis set (FAS): Subjects who received the IMP at least once and had baseline and Week 12 data on monthly average number of headache days of at least moderate severity &quot;Overall Number of Participants Analyzed&quot; = the number of subjects meeting responder criteria</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="54"/>
                <count group_id="O2" value="55"/>
                <count group_id="O3" value="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29.0"/>
                    <measurement group_id="O2" value="29.1"/>
                    <measurement group_id="O3" value="13.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change From Baseline in the Monthly Average Number of Days With Use of Any Acute Headache Medications During the 12-week Period After the First Dose of IMP</title>
        <description>Headache-related efficacy endpoints were derived from headache variables collected using an eDiary. On each day, subjects entered headache data in the electronic headache diary for the previous 24-hour period. Subjects who had experienced headache on the previous day answered questions about the headache (ie, occurrence of headache, duration of headache, maximum severity of headache, presence/absence of associated symptoms, and use of acute headache medications).</description>
        <time_frame>Baseline, 12 weeks</time_frame>
        <population>Full Analysis set (FAS): Subjects who received the IMP at least once and had baseline and Week 12 data on monthly average number of headache days of at least moderate severity</population>
        <group_list>
          <group group_id="O1">
            <title>TEV-48125 (675/225/225 mg) Group</title>
            <description>TEV-48125 will be subcutaneously administered once monthly for 3 months (675/225/225 mg).</description>
          </group>
          <group group_id="O2">
            <title>TEV-48125 (675 mg/Placebo/Placebo) Group</title>
            <description>TEV-48125 or placebo will be subcutaneously administered once monthly for 3 months (675 mg/ placebo/placebo).</description>
          </group>
          <group group_id="O3">
            <title>Placebo Group</title>
            <description>Placebo will be subcutaneously administered once monthly for 3 months (placebo/placebo/placebo).</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change From Baseline in the Monthly Average Number of Days With Use of Any Acute Headache Medications During the 12-week Period After the First Dose of IMP</title>
          <description>Headache-related efficacy endpoints were derived from headache variables collected using an eDiary. On each day, subjects entered headache data in the electronic headache diary for the previous 24-hour period. Subjects who had experienced headache on the previous day answered questions about the headache (ie, occurrence of headache, duration of headache, maximum severity of headache, presence/absence of associated symptoms, and use of acute headache medications).</description>
          <population>Full Analysis set (FAS): Subjects who received the IMP at least once and had baseline and Week 12 data on monthly average number of headache days of at least moderate severity</population>
          <units>days/month</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="187"/>
                <count group_id="O2" value="189"/>
                <count group_id="O3" value="190"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.74" spread="0.44"/>
                    <measurement group_id="O2" value="-3.87" spread="0.43"/>
                    <measurement group_id="O3" value="-2.44" spread="0.43"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change From Baseline in the Monthly Average Number of Headache Days of at Least Moderate Severity During the 12-week Period After the First Dose of IMP in Subjects Not Receiving Concomitant Preventive Migraine Medications</title>
        <description>Headache-related efficacy endpoints were derived from headache variables collected using an eDiary. On each day, subjects entered headache data in the electronic headache diary for the previous 24-hour period. Subjects who had experienced headache on the previous day answered questions about the headache (ie, occurrence of headache, duration of headache, maximum severity of headache, presence/absence of associated symptoms, and use of acute headache medications). Overall headache duration was recorded numerically, in hours, as well as number of hours with headache of at least moderate severity. If headache was reported, then headache severity was subjectively rated by the subject as mild, moderate, or severe.&#xD;
Subjects also recorded the presence or absence of photophobia, phonophobia, nausea, or vomiting, and the status of use of any acute headache medications.&quot;</description>
        <time_frame>Baseline, 12 weeks</time_frame>
        <population>Full Analysis set (FAS): Subjects who received the IMP at least once and had baseline and Week 12 data on monthly average number of headache days of at least moderate severity</population>
        <group_list>
          <group group_id="O1">
            <title>TEV-48125 (675/225/225 mg) Group</title>
            <description>TEV-48125 will be subcutaneously administered once monthly for 3 months (675/225/225 mg).</description>
          </group>
          <group group_id="O2">
            <title>TEV-48125 (675 mg/Placebo/Placebo) Group</title>
            <description>TEV-48125 or placebo will be subcutaneously administered once monthly for 3 months (675 mg/ placebo/placebo).</description>
          </group>
          <group group_id="O3">
            <title>Placebo Group</title>
            <description>Placebo will be subcutaneously administered once monthly for 3 months (placebo/placebo/placebo).</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change From Baseline in the Monthly Average Number of Headache Days of at Least Moderate Severity During the 12-week Period After the First Dose of IMP in Subjects Not Receiving Concomitant Preventive Migraine Medications</title>
          <description>Headache-related efficacy endpoints were derived from headache variables collected using an eDiary. On each day, subjects entered headache data in the electronic headache diary for the previous 24-hour period. Subjects who had experienced headache on the previous day answered questions about the headache (ie, occurrence of headache, duration of headache, maximum severity of headache, presence/absence of associated symptoms, and use of acute headache medications). Overall headache duration was recorded numerically, in hours, as well as number of hours with headache of at least moderate severity. If headache was reported, then headache severity was subjectively rated by the subject as mild, moderate, or severe.&#xD;
Subjects also recorded the presence or absence of photophobia, phonophobia, nausea, or vomiting, and the status of use of any acute headache medications.&quot;</description>
          <population>Full Analysis set (FAS): Subjects who received the IMP at least once and had baseline and Week 12 data on monthly average number of headache days of at least moderate severity</population>
          <units>days/month</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="149"/>
                <count group_id="O2" value="149"/>
                <count group_id="O3" value="149"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.74" spread="0.44"/>
                    <measurement group_id="O2" value="-3.87" spread="0.43"/>
                    <measurement group_id="O3" value="-2.44" spread="0.43"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change From Baseline in Disability Score, as Measured by 6-Item Headache Impact Test (HIT-6) at 4 Weeks After the Final (Third) Dose of IMP</title>
        <description>Subjects assessed the impact of headache on social functioning, role functioning, vitality, cognitive functioning, and psychological distress, using the HIT-6. The HIT-6 total score will be obtained from summation of the 6 question points.Each question is answered on the scale ranging with the following response options: 6 points (never), 8 points (rarely), 10 points (sometimes), 11 points (very often), and 13 points (always).</description>
        <time_frame>Baseline, 4 weeks</time_frame>
        <population>Full Analysis set (FAS): Subjects who received the IMP at least once and had baseline and Week 12 data on monthly average number of headache days of at least moderate severity</population>
        <group_list>
          <group group_id="O1">
            <title>TEV-48125 (675/225/225 mg) Group</title>
            <description>TEV-48125 will be subcutaneously administered once monthly for 3 months (675/225/225 mg).</description>
          </group>
          <group group_id="O2">
            <title>TEV-48125 (675 mg/Placebo/Placebo) Group</title>
            <description>TEV-48125 or placebo will be subcutaneously administered once monthly for 3 months (675 mg/ placebo/placebo).</description>
          </group>
          <group group_id="O3">
            <title>Placebo Group</title>
            <description>Placebo will be subcutaneously administered once monthly for 3 months (placebo/placebo/placebo).</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change From Baseline in Disability Score, as Measured by 6-Item Headache Impact Test (HIT-6) at 4 Weeks After the Final (Third) Dose of IMP</title>
          <description>Subjects assessed the impact of headache on social functioning, role functioning, vitality, cognitive functioning, and psychological distress, using the HIT-6. The HIT-6 total score will be obtained from summation of the 6 question points.Each question is answered on the scale ranging with the following response options: 6 points (never), 8 points (rarely), 10 points (sometimes), 11 points (very often), and 13 points (always).</description>
          <population>Full Analysis set (FAS): Subjects who received the IMP at least once and had baseline and Week 12 data on monthly average number of headache days of at least moderate severity</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="182"/>
                <count group_id="O2" value="180"/>
                <count group_id="O3" value="179"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-8.06" spread="0.70"/>
                    <measurement group_id="O2" value="-8.03" spread="0.68"/>
                    <measurement group_id="O3" value="-6.49" spread="0.68"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Double-blind treatment period (12 weeks)</time_frame>
      <desc>Safety set (SS):Subjects who received the IMP at least once</desc>
      <group_list>
        <group group_id="E1">
          <title>TEV-48125 (675/225/225 mg) Group</title>
          <description>TEV-48125 will be subcutaneously administered once monthly for 3 months (675/225/225 mg).</description>
        </group>
        <group group_id="E2">
          <title>TEV-48125 (675 mg/Placebo/Placebo) Group</title>
          <description>TEV-48125 or placebo will be subcutaneously administered once monthly for 3 months (675 mg/ placebo/placebo).</description>
        </group>
        <group group_id="E3">
          <title>Placebo Group</title>
          <description>Placebo will be subcutaneously administered once monthly for 3 months (placebo/placebo/placebo).</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA Ver. 22.0</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="191"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Intestinal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Brain contusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Breast cancer</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="191"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Asthma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA Ver. 22.0</default_vocab>
        <default_assessment>Non-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="115" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="116" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="117" subjects_at_risk="191"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Iron deficiency anaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Lymphadenitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="191"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Palpitations</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Prinzmetal angina</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Bundle branch block right</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Left ventricular hypertrophy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Deafness neurosensory</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Vertigo</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Meniere's disease</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Tinnitus</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Dry eye</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Astigmatism</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Conjunctival cyst</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Conjunctivitis allergic</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Ocular discomfort</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Asthenopia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Blepharospasm</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Chalazion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Retinopathy solar</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Chronic gastritis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Gastrooesophageal reflux disease</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Tooth loss</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Abdominal discomfort</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Cheilitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Enterocolitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Gastritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Toothache</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Anal fissure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Colitis ischaemic</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Dental caries</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Epigastric discomfort</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Gastric polyps</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Haemorrhoids</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Irritable bowel syndrome</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Lumbar hernia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Periodontal inflammation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Salivary gland mass</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Stomatitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Injection site induration</sub_title>
                <counts group_id="E1" subjects_affected="33" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="23" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="24" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Injection site erythema</sub_title>
                <counts group_id="E1" subjects_affected="29" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="23" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="21" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Injection site pain</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="24" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="17" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Injection site pruritus</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Injection site swelling</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Injection site haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Injection site rash</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Chest pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Generalised oedema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Injection site bruising</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Injection site dermatitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Injection site inflammation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Thirst</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Seasonal allergy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="30" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="40" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="36" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Herpes virus infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Conjunctivitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Gingivitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Kaposi's varicelliform eruption</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Oral herpes</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Tonsillitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Vulvitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Cystitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Helicobacter infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Herpes simplex</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Hordeolum</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Parotitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Pharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Pharyngotonsillitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Pulpitis dental</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Streptococcal infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="191"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Stab wound</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Wound</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Arthropod sting</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Dental restoration failure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Ligament sprain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Muscle contusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Post-traumatic neck syndrome</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Procedural pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Urine leukocyte esterase positive</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Blood urine present</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Gamma-glutamyltransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Blood creatine phosphokinase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Blood glucose increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Blood potassium increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Blood pressure increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Eosinophil count increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Weight increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>White blood cell count increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="191"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperglycaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Vitamin D deficiency</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Diabetic complication</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="191"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Musculoskeletal pain</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Neck pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Musculoskeletal stiffness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Temporomandibular joint syndrome</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Tenosynovitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Limb discomfort</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Osteoarthritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Osteopenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Spinal deformity</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Spondylolisthesis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Cognitive disorder</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Hypersomnia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Hypoaesthesia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Migraine</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Monoplegia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Paraesthesia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Presyncope</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Amnestic disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Dizziness postural</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Intercostal neuralgia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Memory impairment</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Neuralgia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="191"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Alcoholic hangover</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Mental fatigue</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Panic disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Sleep disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Suicidal ideation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="191"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Haematuria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Proteinuria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="191"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Dysmenorrhoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Menorrhagia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Vaginal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Premenstrual syndrome</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="191"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Asthma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Rhinitis allergic</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Reflux laryngitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Throat tightness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract inflammation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Eczema</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Dermatitis contact</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Drug eruption</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Miliaria</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Urticaria</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Erythema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Onycholysis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Seborrhoeic dermatitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Solar dermatitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Peripheral coldness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
              <event>
                <sub_title>Neurogenic shock</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="190"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="191"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Director of Clinical Trials</name_or_title>
      <organization>Otsuka Pharmaceutical Co., LTD.</organization>
      <phone>+81-3-6361-7366</phone>
      <email>CL_OPCJ_RDA_Team@otsuka.jp</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/NCT03303079
org study id: 406-102-00001
secondary id: JapicCTI-173723
nct id: NCT03303079
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
To evaluate the efficacy and safety of subcutaneous (SC) administration of TEV-48125 [monthly
      TEV-48125 225 mg (loading dose only: 675 mg) and TEV-48125 675 mg once over a period of 3
      months] compared with placebo for preventive treatment in Chronic Migraine patients
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Mean Change From Baseline in the Monthly (28 Day) Average Number of Headache Days of at Least Moderate Severity During the 12-week Period After the First Dose of Investigational Medicinal Product (IMP)
time frame: Baseline, 12 weeks
description: Headache-related efficacy endpoints were derived from headache variables collected using an eDiary. On each day, subjects entered headache data in the electronic headache diary for the previous 24-hour period. Subjects who had experienced headache on the previous day answered questions about the headache (ie, occurrence of headache, duration of headache, maximum severity of headache, presence/absence of associated symptoms, and use of acute headache medications). Overall headache duration was recorded numerically, in hours, as well as number of hours with headache of at least moderate severity. If headache was reported, then headache severity was subjectively rated by the subject as mild, moderate, or severe.
Subjects also recorded the presence or absence of photophobia, phonophobia, nausea, or vomiting, and the status of use of any acute headache medications.
measure: Mean Change From Baseline in the Monthly Average Number of Migraine Days During the 12-week Period After the First Dose of IMP
time frame: Baseline, 12 weeks
description: Headache-related efficacy endpoints were derived from headache variables collected using an eDiary. On each day, subjects entered headache data in the electronic headache diary for the previous 24-hour period. Subjects who had experienced headache on the previous day answered questions about the headache (ie, occurrence of headache, duration of headache, maximum severity of headache, presence/absence of associated symptoms, and use of acute headache medications). Overall headache duration was recorded numerically, in hours, as well as number of hours with headache of at least moderate severity. If headache was reported, then headache severity was subjectively rated by the subject as mild, moderate, or severe.
Subjects also recorded the presence or absence of photophobia, phonophobia, nausea, or vomiting, and the status of use of any acute headache medications.
measure: Proportion of Subjects Reaching at Least 50% Reduction in the Monthly Average Number of Headache Days of at Least Moderate Severity During the 12-week Period After the First Dose of IMP
time frame: 12 weeks
description: Headache-related efficacy endpoints were derived from headache variables collected using an eDiary. On each day, subjects entered headache data in the electronic headache diary for the previous 24-hour period. Subjects who had experienced headache on the previous day answered questions about the headache (ie, occurrence of headache, duration of headache, maximum severity of headache, presence/absence of associated symptoms, and use of acute headache medications). Overall headache duration was recorded numerically, in hours, as well as number of hours with headache of at least moderate severity. If headache was reported, then headache severity was subjectively rated by the subject as mild, moderate, or severe.
Subjects also recorded the presence or absence of photophobia, phonophobia, nausea, or vomiting, and the status of use of any acute headache medications.
measure: Mean Change From Baseline in the Monthly Average Number of Days With Use of Any Acute Headache Medications During the 12-week Period After the First Dose of IMP
time frame: Baseline, 12 weeks
description: Headache-related efficacy endpoints were derived from headache variables collected using an eDiary. On each day, subjects entered headache data in the electronic headache diary for the previous 24-hour period. Subjects who had experienced headache on the previous day answered questions about the headache (ie, occurrence of headache, duration of headache, maximum severity of headache, presence/absence of associated symptoms, and use of acute headache medications).
measure: Mean Change From Baseline in the Monthly Average Number of Headache Days of at Least Moderate Severity During the 12-week Period After the First Dose of IMP in Subjects Not Receiving Concomitant Preventive Migraine Medications
time frame: Baseline, 12 weeks
description: Headache-related efficacy endpoints were derived from headache variables collected using an eDiary. On each day, subjects entered headache data in the electronic headache diary for the previous 24-hour period. Subjects who had experienced headache on the previous day answered questions about the headache (ie, occurrence of headache, duration of headache, maximum severity of headache, presence/absence of associated symptoms, and use of acute headache medications). Overall headache duration was recorded numerically, in hours, as well as number of hours with headache of at least moderate severity. If headache was reported, then headache severity was subjectively rated by the subject as mild, moderate, or severe.
Subjects also recorded the presence or absence of photophobia, phonophobia, nausea, or vomiting, and the status of use of any acute headache medications."
measure: Mean Change From Baseline in Disability Score, as Measured by 6-Item Headache Impact Test (HIT-6) at 4 Weeks After the Final (Third) Dose of IMP
time frame: Baseline, 4 weeks
description: Subjects assessed the impact of headache on social functioning, role functioning, vitality, cognitive functioning, and psychological distress, using the HIT-6. The HIT-6 total score will be obtained from summation of the 6 question points.Each question is answered on the scale ranging with the following response options: 6 points (never), 8 points (rarely), 10 points (sometimes), 11 points (very often), and 13 points (always).
arm group label: TEV-48125 (675/225/225 mg) group
arm group type: Experimental
description: TEV-48125 will be subcutaneously administered once monthly for 3 months (675/225/225 mg).
arm group label: TEV-48125 (675 mg/placebo/placebo) group
arm group type: Experimental
description: TEV-48125 or placebo will be subcutaneously administered once monthly for 3 months (675 mg/ placebo/placebo).
arm group label: Placebo group
arm group type: Placebo Comparator
description: Placebo will be subcutaneously administered once monthly for 3 months (placebo/placebo/placebo).
intervention type: Drug
intervention name: TEV-48125
description: TEV-48125 will be subcutaneously administered once monthly for 3 months.
arm group label: TEV-48125 (675/225/225 mg) group
intervention type: Drug
intervention name: TEV-48125 or placebo
description: TEV-48125 or placebo will be subcutaneously administered once monthly for 3 months.
arm group label: TEV-48125 (675 mg/placebo/placebo) group
intervention type: Drug
intervention name: Placebo
description: Placebo will be subcutaneously administered once monthly for 3 months.
arm group label: Placebo group
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Takehisa Matsumaru
role: Study Director
affiliation: Otsuka Pharmaceutical Co., Ltd.
facility: 
country: Japan
responsible party type: Sponsor
mesh term: Migraine Disorders
mesh term: Antibodies, Monoclonal
sharing ipd: Undecided
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 