<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/NCT03303105</url>
  </required_header>
  <id_info>
    <org_study_id>406-102-00003</org_study_id>
    <secondary_id>JapicCTI-173726</secondary_id>
    <nct_id>NCT03303105</nct_id>
  </id_info>
  <brief_title>Long-term Safety and Tolerability of Subcutaneous Administration of TEV-48125 for the Preventive Treatment of Migraine</brief_title>
  <official_title>A Multicenter, Randomized, Open-label Trial Evaluating the Long-term Safety and Tolerability of Subcutaneous Administration of TEV-48125 for the Preventive Treatment of 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 long-term safety and tolerability of subcutaneous (SC) administration of&#xD;
      TEV-48125 (at 225 mg once monthly [except for a loading dose of 675 mg for CM patients] or at&#xD;
      675 mg every 3 months) for the preventive treatment of Chronic Migraine and Episodic Migraine&#xD;
      patients&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 7, 2017</start_date>
  <completion_date type="Actual">June 16, 2020</completion_date>
  <primary_completion_date type="Actual">June 16, 2020</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of Subjects With at Least One Treatment-Emergent Adverse Event (TEAE)</measure>
    <time_frame>Baseline (Day 0) up to follow-up visit (Day 562)</time_frame>
    <description>TEAEs are defined as the AEs that started after trial investigational medicinal product (IMP) treatment. Multiple occurrences of TEAEs are counted once per MedDRA preferred term.&#xD;
Specific AE terms are provided in the Adverse Event section.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mean Change From Baseline in the Monthly (28 Day) Average Number of Migraine Days</measure>
    <time_frame>Baseline, Month 12</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 (28 Day) Average Number of Headache Days of at Least Moderate Severity</measure>
    <time_frame>Baseline, Month 12</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>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">50</enrollment>
  <condition>Migraine</condition>
  <arm_group>
    <arm_group_label>TEV-48125 (225 mg/1 month) group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>TEV-48125 will be administered subcutaneously once every 4 weeks for a total of 13 doses (at 225 mg once monthly [except for a loading dose of 675 mg in subjects with CM]).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>TEV-48125 (675 mg/3 month) group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>TEV-48125 will be administered subcutaneously once every 12 weeks for a total of 5 doses (at 675 mg once every 3 months).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TEV-48125</intervention_name>
    <description>TEV-48125 will be administered subcutaneously once every 4 weeks.</description>
    <arm_group_label>TEV-48125 (225 mg/1 month) group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TEV-48125</intervention_name>
    <description>TEV-48125 will be administered subcutaneously once every 12 weeks.</description>
    <arm_group_label>TEV-48125 (675 mg/3 month) 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 or Episodic migraine in baseline&#xD;
             information collected 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 2 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;
        - Hematological, cardiac, renal, endocrine, pulmonary, gastrointestinal, genitourinary,&#xD;
        neurologic, hepatic, or ocular disease considered clinically significant in the judgment of&#xD;
        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>February 2023</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>June 27, 2021</results_first_submitted>
  <results_first_submitted_qc>June 27, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">July 16, 2021</results_first_posted>
  <last_update_submitted>February 16, 2023</last_update_submitted>
  <last_update_submitted_qc>February 16, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 17, 2023</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/05/NCT03303105/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 11, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/05/NCT03303105/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>TEV-48125 (225 mg/1 Month) Group</title>
          <description>TEV-48125 will be administered subcutaneously once every 4 weeks for a total of 13 doses (at 225 mg once monthly [except for a loading dose of 675 mg in subjects with chronic migraine).</description>
        </group>
        <group group_id="P2">
          <title>TEV-48125 (675 mg/3 Month) Group</title>
          <description>TEV-48125 will be administered subcutaneously once every 12 weeks for a total of 5 doses (at 675 mg once every 3 months).</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="25"/>
                <participants group_id="P2" count="25"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="23"/>
                <participants group_id="P2" count="21"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="4"/>
              </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="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>TEV-48125 (225 mg/1 Month) Group</title>
          <description>TEV-48125 will be administered subcutaneously once every 4 weeks for a total of 13 doses (at 225 mg once monthly [except for a loading dose of 675 mg in subjects with chronic migraine).</description>
        </group>
        <group group_id="B2">
          <title>TEV-48125 (675 mg/3 Month) Group</title>
          <description>TEV-48125 will be administered subcutaneously once every 12 weeks for a total of 5 doses (at 675 mg once every 3 months).</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="25"/>
            <count group_id="B2" value="25"/>
            <count group_id="B3" value="50"/>
          </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_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="24"/>
                    <measurement group_id="B2" value="25"/>
                    <measurement group_id="B3" value="49"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </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="46.8" spread="7.9"/>
                    <measurement group_id="B2" value="45.8" spread="7.0"/>
                    <measurement group_id="B3" value="46.3" spread="7.4"/>
                  </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="23"/>
                    <measurement group_id="B2" value="19"/>
                    <measurement group_id="B3" value="42"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="8"/>
                  </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>Japanese</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="25"/>
                    <measurement group_id="B2" value="25"/>
                    <measurement group_id="B3" value="50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Japan</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="25"/>
                    <measurement group_id="B2" value="25"/>
                    <measurement group_id="B3" value="50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Subjects With at Least One Treatment-Emergent Adverse Event (TEAE)</title>
        <description>TEAEs are defined as the AEs that started after trial investigational medicinal product (IMP) treatment. Multiple occurrences of TEAEs are counted once per MedDRA preferred term.&#xD;
Specific AE terms are provided in the Adverse Event section.</description>
        <time_frame>Baseline (Day 0) up to follow-up visit (Day 562)</time_frame>
        <population>Safety Set (SS): Newly enrolled subjects who received the IMP at least once</population>
        <group_list>
          <group group_id="O1">
            <title>TEV-48125 (225 mg/1 Month) Group</title>
            <description>TEV-48125 will be administered subcutaneously once every 4 weeks for a total of 13 doses (at 225 mg once monthly [except for a loading dose of 675 mg in subjects with chronic migraine).</description>
          </group>
          <group group_id="O2">
            <title>TEV-48125 (675 mg/3 Month) Group</title>
            <description>TEV-48125 will be administered subcutaneously once every 12 weeks for a total of 5 doses (at 675 mg once every 3 months).</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Subjects With at Least One Treatment-Emergent Adverse Event (TEAE)</title>
          <description>TEAEs are defined as the AEs that started after trial investigational medicinal product (IMP) treatment. Multiple occurrences of TEAEs are counted once per MedDRA preferred term.&#xD;
Specific AE terms are provided in the Adverse Event section.</description>
          <population>Safety Set (SS): Newly enrolled subjects who received the IMP at least once</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="25"/>
                <count group_id="O2" value="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="92.0"/>
                    <measurement group_id="O2" value="88.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change From Baseline in the Monthly (28 Day) Average Number of Migraine Days</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, Month 12</time_frame>
        <population>Full Analysis set (FAS): Newly enrolled subjects for whom electronic headache diary efficacy assessment data at baseline and after the first dose of IMP were available</population>
        <group_list>
          <group group_id="O1">
            <title>TEV-48125 (225 mg/1 Month) Group</title>
            <description>TEV-48125 will be administered subcutaneously once every 4 weeks for a total of 13 doses (at 225 mg once monthly [except for a loading dose of 675 mg in subjects with chronic migraine).</description>
          </group>
          <group group_id="O2">
            <title>TEV-48125 (675 mg/3 Month) Group</title>
            <description>TEV-48125 will be administered subcutaneously once every 12 weeks for a total of 5 doses (at 675 mg once every 3 months).</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change From Baseline in the Monthly (28 Day) Average Number of Migraine Days</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): Newly enrolled subjects for whom electronic headache diary efficacy assessment data at baseline and after the first dose of IMP were available</population>
          <units>days/month</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="23"/>
                <count group_id="O2" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-5.9" spread="4.3"/>
                    <measurement group_id="O2" value="-1.6" spread="5.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change From Baseline in the Monthly (28 Day) Average Number of Headache Days of at Least Moderate Severity</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, Month 12</time_frame>
        <population>Full Analysis set (FAS): Newly enrolled subjects for whom electronic headache diary efficacy assessment data at baseline and after the first dose of IMP were available</population>
        <group_list>
          <group group_id="O1">
            <title>TEV-48125 (225 mg/1 Month) Group</title>
            <description>TEV-48125 will be administered subcutaneously once every 4 weeks for a total of 13 doses (at 225 mg once monthly [except for a loading dose of 675 mg in subjects with chronic migraine).</description>
          </group>
          <group group_id="O2">
            <title>TEV-48125 (675 mg/3 Month) Group</title>
            <description>TEV-48125 will be administered subcutaneously once every 12 weeks for a total of 5 doses (at 675 mg once every 3 months).</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</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): Newly enrolled subjects for whom electronic headache diary efficacy assessment data at baseline and after the first dose of IMP were available</population>
          <units>days/month</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="23"/>
                <count group_id="O2" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.3" spread="4.1"/>
                    <measurement group_id="O2" value="-2.1" spread="4.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Baseline (Day 0) up to follow-up visit (Day 562)</time_frame>
      <desc>Safety Set (SS): Newly enrolled subjects who received the IMP at least once</desc>
      <group_list>
        <group group_id="E1">
          <title>TEV-48125 (225 mg/1 Month) Group</title>
          <description>TEV-48125 will be administered subcutaneously once every 4 weeks for a total of 13 doses (at 225 mg once monthly [except for a loading dose of 675 mg in subjects with chronic migraine).</description>
        </group>
        <group group_id="E2">
          <title>TEV-48125 (675 mg/3 Month) Group</title>
          <description>TEV-48125 will be administered subcutaneously once every 12 weeks for a total of 5 doses (at 675 mg once every 3 months).</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="25"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Rhegmatogenous retinal detachment</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Subarachnoid haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</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="20" subjects_at_risk="25"/>
                <counts group_id="E2" subjects_affected="16" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Injection site pruritus</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="25"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Injection site induration</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="25"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Injection site erythema</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="25"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Injection site pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="25"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Oral herpes</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="18" subjects_at_risk="25"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="25"/>
              </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="1" subjects_at_risk="25"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="25"/>
              </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="2" subjects_at_risk="25"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="25"/>
              </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/NCT03303105
org study id: 406-102-00003
secondary id: JapicCTI-173726
nct id: NCT03303105
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
To evaluate the long-term safety and tolerability of subcutaneous (SC) administration of
      TEV-48125 (at 225 mg once monthly [except for a loading dose of 675 mg for CM patients] or at
      675 mg every 3 months) for the preventive treatment of Chronic Migraine and Episodic Migraine
      patients
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percentage of Subjects With at Least One Treatment-Emergent Adverse Event (TEAE)
time frame: Baseline (Day 0) up to follow-up visit (Day 562)
description: TEAEs are defined as the AEs that started after trial investigational medicinal product (IMP) treatment. Multiple occurrences of TEAEs are counted once per MedDRA preferred term.
Specific AE terms are provided in the Adverse Event section.
measure: Mean Change From Baseline in the Monthly (28 Day) Average Number of Migraine Days
time frame: Baseline, Month 12
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 (28 Day) Average Number of Headache Days of at Least Moderate Severity
time frame: Baseline, Month 12
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.
arm group label: TEV-48125 (225 mg/1 month) group
arm group type: Experimental
description: TEV-48125 will be administered subcutaneously once every 4 weeks for a total of 13 doses (at 225 mg once monthly [except for a loading dose of 675 mg in subjects with CM]).
arm group label: TEV-48125 (675 mg/3 month) group
arm group type: Experimental
description: TEV-48125 will be administered subcutaneously once every 12 weeks for a total of 5 doses (at 675 mg once every 3 months).
intervention type: Drug
intervention name: TEV-48125
description: TEV-48125 will be administered subcutaneously once every 4 weeks.
arm group label: TEV-48125 (225 mg/1 month) group
intervention type: Drug
intervention name: TEV-48125
description: TEV-48125 will be administered subcutaneously once every 12 weeks.
arm group label: TEV-48125 (675 mg/3 month) 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: 