<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/NCT03228433</url>
  </required_header>
  <id_info>
    <org_study_id>TAK-418-1001</org_study_id>
    <secondary_id>U1111-1195-7777</secondary_id>
    <nct_id>NCT03228433</nct_id>
  </id_info>
  <brief_title>A Study to Evaluate Safety, Tolerability and Pharmacokinetics of Ascending Oral Single Dose of TAK-418 in Healthy Participants</brief_title>
  <official_title>A Randomized, Double-Blind, Placebo-Controlled, Ascending Oral Single Dose Trial to Evaluate the Safety, Tolerability, and Pharmacokinetics of TAK-418 in Healthy Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Takeda</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Takeda</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the safety and tolerability of TAK-418 following&#xD;
      single oral doses in healthy participants.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The drug being tested in this study is called TAK-418. TAK-418 is being tested in healthy&#xD;
      participants in order to evaluate the safety, tolerability, and pharmacokinetics (PK) of&#xD;
      single oral doses.&#xD;
&#xD;
      The study will enroll approximately 40 healthy participants. The study consists of equally&#xD;
      divided 5 sequential cohorts of 8 participants each. In each of the following cohorts, 6&#xD;
      participants will be randomized to receive TAK-418 and 2 participants will receive matching&#xD;
      placebo-which will remain undisclosed to the participant and study doctor during the study&#xD;
      (unless there is an urgent medical need):&#xD;
&#xD;
        -  Cohort 1: TAK-418 5 mg&#xD;
&#xD;
        -  Cohort 2: TAK-418 15 mg&#xD;
&#xD;
        -  Cohort 3: TAK-418 30 mg Fasted + TAK-418 30 mg Fed&#xD;
&#xD;
        -  Cohort 4: TAK-418 40 mg&#xD;
&#xD;
        -  Cohort 5: TAK-418 60 mg&#xD;
&#xD;
      All participants will be asked to take TAK-418 or placebo-matching capsule once on Day 1 in&#xD;
      each cohort. A washout period of 28-days will be maintained between the doses in Cohort 3.&#xD;
&#xD;
      This single center trial will be conducted in the United States. Participants in this study&#xD;
      will be assigned to one of 5 possible dose cohorts. Male participants will return for&#xD;
      additional outpatient visits on Days 91 and 93 (+/- 7 days) and may return for outpatient&#xD;
      visits on Days 182 and 184 (+/- 7 days) (depending on results from the Day 93 Visit).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 21, 2017</start_date>
  <completion_date type="Actual">May 12, 2018</completion_date>
  <primary_completion_date type="Actual">May 12, 2018</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)</measure>
    <time_frame>Baseline Up to Day 184</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants Who Discontinued Due to an Adverse Event (AE)</measure>
    <time_frame>Baseline Up to Day 184</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants Who Meet the Markedly Abnormal Criteria for Neurological Assessment Measurements at Least Once Post Dose</measure>
    <time_frame>Baseline Up to Day 184</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post Dose</measure>
    <time_frame>Baseline Up to Day 184</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose</measure>
    <time_frame>Baseline Up to day 184</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants Who Meet the Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Parameters at Least Once Post Dose</measure>
    <time_frame>Baseline Up to Day 14</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration of TAK-418F (TAK-418 Free Base)</measure>
    <time_frame>Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-418F</measure>
    <time_frame>Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmax: Maximum Observed Plasma Concentration for TAK-418F</measure>
    <time_frame>Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-418F</measure>
    <time_frame>Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose</time_frame>
    <description>The pharmacokinetic analysis set included all participants who received at least 1 dose of study drug and had at least one measurable plasma concentration or amount of drug in urine for TAK-418-F.</description>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">40</enrollment>
  <condition>Healthy Participants</condition>
  <arm_group>
    <arm_group_label>Cohort 1: TAK-418 5 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>TAK-418 5 milligram (mg), capsule, orally, once on Day 1.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 2: TAK-418 15 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>TAK-418 15 mg, capsule, orally, once on Day 1. Actual dose of TAK-418 may vary based on safety, tolerability and PK data from previous Cohorts.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 3: TAK-418 30 mg Fasted + TAK-418 30 mg Fed</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>TAK-418 30 mg, capsule, in fasted state, orally, once on Day 1, followed by a 28-day washout period, further followed by TAK-418 30 mg, capsule, in fed state, orally, once on Day 1. Actual dose of TAK-418 may vary based on safety, tolerability and PK data from previous Cohorts.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 4: TAK-418 40 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>TAK-418 40 mg, capsule, orally, once on Day 1. Actual dose of TAK-418 may vary based on safety, tolerability and PK data from previous Cohorts.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 5: TAK-418 60 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>TAK-418 60 mg, capsule, orally, once on Day 1. Actual dose of TAK-418 may vary based on safety, tolerability and PK data from previous Cohorts.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohorts 1-5: Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>TAK-418 placebo-matching, capsule, orally, once on Day 1.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TAK-418</intervention_name>
    <description>TAK-418 Capsule.</description>
    <arm_group_label>Cohort 1: TAK-418 5 mg</arm_group_label>
    <arm_group_label>Cohort 2: TAK-418 15 mg</arm_group_label>
    <arm_group_label>Cohort 3: TAK-418 30 mg Fasted + TAK-418 30 mg Fed</arm_group_label>
    <arm_group_label>Cohort 4: TAK-418 40 mg</arm_group_label>
    <arm_group_label>Cohort 5: TAK-418 60 mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TAK-418 Placebo</intervention_name>
    <description>TAK-418 placebo-matching capsules.</description>
    <arm_group_label>Cohorts 1-5: Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Is a male or female participants with a body mass index (BMI) within the range of 18.5&#xD;
             -30.0 kilogram per square meter (kg/m^2) at the Screening Visit.&#xD;
&#xD;
          2. Is a nonsmoker who has not used tobacco or nicotine-containing products (example,&#xD;
             nicotine patch) for at least 6 months before trial drug administration of the initial&#xD;
             dose of trial drug or invasive procedure.&#xD;
&#xD;
          3. Must be judged to be in good health by the investigator, based on clinical evaluations&#xD;
             including laboratory safety tests, medical history, physical examination, 12-lead ECG,&#xD;
             and vital sign measurements performed at the Screening Visit and before administration&#xD;
             of the initial dose of trial drug or invasive procedure as per principal&#xD;
             investigator's judgment.&#xD;
&#xD;
          4. Female subjects with no childbearing potential, defined by at least 1 of the following&#xD;
             criteria:&#xD;
&#xD;
               -  Postmenopausal (defined as 12 months of spontaneous amenorrhea in women aged&#xD;
                  greater than [&gt;]45 years, 6 months of spontaneous amenorrhea in women aged &gt;45&#xD;
                  years with serum follicle-stimulating hormone [FSH] levels &gt;40&#xD;
                  milli-international units per milliliter [mIU/mL]). Appropriate documentation of&#xD;
                  FSH levels is required.&#xD;
&#xD;
               -  Surgically sterile by hysterectomy and/or bilateral oophorectomy with appropriate&#xD;
                  documentation of surgical procedure.&#xD;
&#xD;
               -  Had a tubal ligation with appropriate documentation of surgical procedure.&#xD;
&#xD;
               -  Has a congenital condition resulting in no uterus.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Has had major surgery, donated or lost 1 unit of blood (approximately 500 milliliter&#xD;
             [mL]) within 4 weeks before the Screening Visit.&#xD;
&#xD;
          2. Has a risk of suicide according to the investigator's clinical judgment per the&#xD;
             Columbia-Suicide Severity Rating Scale at Screening or has made a suicide attempt in&#xD;
             the 6 months before Screening.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Medical Director</last_name>
    <role>Study Director</role>
    <affiliation>Takeda</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>PAREXEL International</name>
      <address>
        <city>Glendale</city>
        <state>California</state>
        <zip>91206</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2019</verification_date>
  <study_first_submitted>July 21, 2017</study_first_submitted>
  <study_first_submitted_qc>July 21, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 24, 2017</study_first_posted>
  <results_first_submitted>May 8, 2019</results_first_submitted>
  <results_first_submitted_qc>August 9, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">September 9, 2019</results_first_posted>
  <last_update_submitted>August 9, 2019</last_update_submitted>
  <last_update_submitted_qc>August 9, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">September 9, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Drug Therapy</keyword>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Takeda makes patient-level, de-identified data sets and associated documents available after applicable marketing approvals and commercial availability have been received, an opportunity for the primary publication of the research has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com/Approach for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.</ipd_description>
  </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 7, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/33/NCT03228433/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 7, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/33/NCT03228433/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants took part in the study at single site in the United States from 21 July 2017 to 12 May 2018.</recruitment_details>
      <pre_assignment_details>Healthy participants were randomized to receive TAK-418 or matching placebo in Cohorts 1 to 5.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Cohorts 1-5: Placebo</title>
          <description>TAK-418 placebo-matching, capsule, orally, once on Day 1.</description>
        </group>
        <group group_id="P2">
          <title>Cohort 1: TAK-418 5 mg</title>
          <description>TAK-418 5 milligram (mg), capsule, orally, once on Day 1.</description>
        </group>
        <group group_id="P3">
          <title>Cohort 2: TAK-418 15 mg</title>
          <description>TAK-418 15 mg, capsule, orally, once on Day 1.</description>
        </group>
        <group group_id="P4">
          <title>Cohort 3: TAK-418 30 mg Fasted + TAK-418 30 mg Fed</title>
          <description>TAK-418 30 mg, capsule, in fasted state, orally, once on Day 1, followed by a 28-day washout period, further followed by TAK-418 30 mg, capsule, in fed state, orally, once on Day 1.</description>
        </group>
        <group group_id="P5">
          <title>Cohort 4: TAK-418 40 mg</title>
          <description>TAK-418 40 mg, capsule, orally, once on Day 1.</description>
        </group>
        <group group_id="P6">
          <title>Cohort 5: TAK-418 60 mg</title>
          <description>TAK-418 60 mg, capsule, orally, once on Day 1.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="6"/>
                <participants group_id="P4" count="6"/>
                <participants group_id="P5" count="6"/>
                <participants group_id="P6" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="6"/>
                <participants group_id="P4" count="5"/>
                <participants group_id="P5" count="6"/>
                <participants group_id="P6" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="1"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Positive alcohol test</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="1"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The safety analysis set included all randomized participants who received at least 1 dose of study drug.</population>
      <group_list>
        <group group_id="B1">
          <title>Cohorts 1-5: Placebo</title>
          <description>TAK-418 placebo-matching, capsule, orally, once on Day 1.</description>
        </group>
        <group group_id="B2">
          <title>Cohort 1: TAK-418 5 mg</title>
          <description>TAK-418 5 mg, capsule, orally, once on Day 1.</description>
        </group>
        <group group_id="B3">
          <title>Cohort 2: TAK-418 15 mg</title>
          <description>TAK-418 15 mg, capsule, orally, once on Day 1.</description>
        </group>
        <group group_id="B4">
          <title>Cohort 3: TAK-418 30 mg Fasted + TAK-418 30 mg Fed</title>
          <description>TAK-418 30 mg, capsule, in fasted state, orally, once on Day 1, followed by a 28-day washout period, further followed by TAK-418 30 mg, capsule, in fed state, orally, once on Day 1.</description>
        </group>
        <group group_id="B5">
          <title>Cohort 4: TAK-418 40 mg</title>
          <description>TAK-418 40 mg, capsule, orally, once on Day 1.</description>
        </group>
        <group group_id="B6">
          <title>Cohort 5: TAK-418 60 mg</title>
          <description>TAK-418 60 mg, capsule, orally, once on Day 1.</description>
        </group>
        <group group_id="B7">
          <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="10"/>
            <count group_id="B2" value="6"/>
            <count group_id="B3" value="6"/>
            <count group_id="B4" value="6"/>
            <count group_id="B5" value="6"/>
            <count group_id="B6" value="6"/>
            <count group_id="B7" value="40"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="36.4" spread="9.63"/>
                    <measurement group_id="B2" value="37.2" spread="10.42"/>
                    <measurement group_id="B3" value="33.3" spread="10.80"/>
                    <measurement group_id="B4" value="40.0" spread="10.60"/>
                    <measurement group_id="B5" value="33.2" spread="6.49"/>
                    <measurement group_id="B6" value="38.7" spread="10.03"/>
                    <measurement group_id="B7" value="36.5" spread="9.43"/>
                  </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="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="3"/>
                    <measurement group_id="B7" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="5"/>
                    <measurement group_id="B5" value="6"/>
                    <measurement group_id="B6" value="3"/>
                    <measurement group_id="B7" value="32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="1"/>
                    <measurement group_id="B6" value="1"/>
                    <measurement group_id="B7" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="6"/>
                    <measurement group_id="B5" value="5"/>
                    <measurement group_id="B6" value="5"/>
                    <measurement group_id="B7" value="33"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</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 group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</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 group_id="B5" value="1"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="1"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</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 group_id="B5" value="0"/>
                    <measurement group_id="B6" value="1"/>
                    <measurement group_id="B7" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="2"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="4"/>
                    <measurement group_id="B5" value="2"/>
                    <measurement group_id="B6" value="5"/>
                    <measurement group_id="B7" value="22"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</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="1"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</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 group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                  </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>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="6"/>
                    <measurement group_id="B5" value="6"/>
                    <measurement group_id="B6" value="6"/>
                    <measurement group_id="B7" value="40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Weight</title>
          <units>kilogram (kg)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="81.2" spread="12.34"/>
                    <measurement group_id="B2" value="76.0" spread="13.58"/>
                    <measurement group_id="B3" value="81.8" spread="6.83"/>
                    <measurement group_id="B4" value="82.5" spread="4.22"/>
                    <measurement group_id="B5" value="80.0" spread="12.43"/>
                    <measurement group_id="B6" value="76.1" spread="15.23"/>
                    <measurement group_id="B7" value="79.8" spread="11.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Height</title>
          <units>centimeter (cm)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="173.4" spread="8.66"/>
                    <measurement group_id="B2" value="171.0" spread="8.10"/>
                    <measurement group_id="B3" value="174.8" spread="3.19"/>
                    <measurement group_id="B4" value="172.5" spread="5.09"/>
                    <measurement group_id="B5" value="181.2" spread="5.08"/>
                    <measurement group_id="B6" value="171.5" spread="11.78"/>
                    <measurement group_id="B7" value="174.0" spread="7.89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Body mass index (BMI)</title>
          <units>kilogram per square meter (kg/m^2)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="26.94" spread="3.065"/>
                    <measurement group_id="B2" value="25.82" spread="2.440"/>
                    <measurement group_id="B3" value="26.83" spread="2.835"/>
                    <measurement group_id="B4" value="27.83" spread="2.414"/>
                    <measurement group_id="B5" value="24.32" spread="2.988"/>
                    <measurement group_id="B6" value="25.73" spread="2.992"/>
                    <measurement group_id="B7" value="26.32" spread="2.864"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)</title>
        <time_frame>Baseline Up to Day 184</time_frame>
        <population>The safety analysis set included all randomized participants who received at least 1 dose of study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohorts 1-5: Placebo</title>
            <description>TAK-418 placebo-matching, capsule, orally, once on Day 1.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 1: TAK-418 5 mg</title>
            <description>TAK-418 5 mg, capsule, orally, once on Day 1.</description>
          </group>
          <group group_id="O3">
            <title>Cohort 2: TAK-418 15 mg</title>
            <description>TAK-418 15 mg, capsule, orally, once on Day 1.</description>
          </group>
          <group group_id="O4">
            <title>Cohort 3A: TAK-418 30 mg Fasted</title>
            <description>TAK-418 30 mg, capsule, in fasted state, orally, once on Day 1.</description>
          </group>
          <group group_id="O5">
            <title>Cohort 3B: TAK-418 30 mg Fed</title>
            <description>TAK-418 30 mg, capsule, in fed state, orally, once on Day 1.</description>
          </group>
          <group group_id="O6">
            <title>Cohort 4: TAK-418 40 mg</title>
            <description>TAK-418 40 mg, capsule, orally, once on Day 1.</description>
          </group>
          <group group_id="O7">
            <title>Cohort 5: TAK-418 60 mg</title>
            <description>TAK-418 60 mg, capsule, orally, once on Day 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)</title>
          <population>The safety analysis set included all randomized participants who received at least 1 dose of study drug.</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="6"/>
                <count group_id="O5" value="5"/>
                <count group_id="O6" value="6"/>
                <count group_id="O7" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="2"/>
                    <measurement group_id="O4" value="3"/>
                    <measurement group_id="O5" value="1"/>
                    <measurement group_id="O6" value="3"/>
                    <measurement group_id="O7" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants Who Discontinued Due to an Adverse Event (AE)</title>
        <time_frame>Baseline Up to Day 184</time_frame>
        <population>The safety analysis set included all randomized participants who received at least 1 dose of study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohorts 1-5: Placebo</title>
            <description>TAK-418 placebo-matching, capsule, orally, once on Day 1.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 1: TAK-418 5 mg</title>
            <description>TAK-418 5 mg, capsule, orally, once on Day 1.</description>
          </group>
          <group group_id="O3">
            <title>Cohort 2: TAK-418 15 mg</title>
            <description>TAK-418 15 mg, capsule, orally, once on Day 1.</description>
          </group>
          <group group_id="O4">
            <title>Cohort 3A: TAK-418 30 mg Fasted</title>
            <description>TAK-418 30 mg, capsule, in fasted state, orally, once on Day 1.</description>
          </group>
          <group group_id="O5">
            <title>Cohort 3B: TAK-418 30 mg Fed</title>
            <description>TAK-418 30 mg, capsule, in fed state, orally, once on Day 1.</description>
          </group>
          <group group_id="O6">
            <title>Cohort 4: TAK-418 40 mg</title>
            <description>TAK-418 40 mg, capsule, orally, once on Day 1.</description>
          </group>
          <group group_id="O7">
            <title>Cohort 5: TAK-418 60 mg</title>
            <description>TAK-418 60 mg, capsule, orally, once on Day 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Who Discontinued Due to an Adverse Event (AE)</title>
          <population>The safety analysis set included all randomized participants who received at least 1 dose of study drug.</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="6"/>
                <count group_id="O5" value="5"/>
                <count group_id="O6" value="6"/>
                <count group_id="O7" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="0"/>
                    <measurement group_id="O7" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants Who Meet the Markedly Abnormal Criteria for Neurological Assessment Measurements at Least Once Post Dose</title>
        <time_frame>Baseline Up to Day 184</time_frame>
        <population>The safety analysis set included all randomized participants who received at least 1 dose of study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohorts 1-5: Placebo</title>
            <description>TAK-418 placebo-matching, capsule, orally, once on Day 1.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 1: TAK-418 5 mg</title>
            <description>TAK-418 5 mg, capsule, orally, once on Day 1.</description>
          </group>
          <group group_id="O3">
            <title>Cohort 2: TAK-418 15 mg</title>
            <description>TAK-418 15 mg, capsule, orally, once on Day 1.</description>
          </group>
          <group group_id="O4">
            <title>Cohort 3A: TAK-418 30 mg Fasted</title>
            <description>TAK-418 30 mg, capsule, in fasted state, orally, once on Day 1.</description>
          </group>
          <group group_id="O5">
            <title>Cohort 3B: TAK-418 30 mg Fed</title>
            <description>TAK-418 30 mg, capsule, in fed state, orally, once on Day 1.</description>
          </group>
          <group group_id="O6">
            <title>Cohort 4: TAK-418 40 mg</title>
            <description>TAK-418 40 mg, capsule, orally, once on Day 1.</description>
          </group>
          <group group_id="O7">
            <title>Cohort 5: TAK-418 60 mg</title>
            <description>TAK-418 60 mg, capsule, orally, once on Day 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Who Meet the Markedly Abnormal Criteria for Neurological Assessment Measurements at Least Once Post Dose</title>
          <population>The safety analysis set included all randomized participants who received at least 1 dose of study drug.</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="6"/>
                <count group_id="O5" value="5"/>
                <count group_id="O6" value="6"/>
                <count group_id="O7" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="0"/>
                    <measurement group_id="O7" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post Dose</title>
        <time_frame>Baseline Up to Day 184</time_frame>
        <population>The safety analysis set included all randomized participants who received at least 1 dose of study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohorts 1-5: Placebo</title>
            <description>TAK-418 placebo-matching, capsule, orally, once on Day 1.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 1: TAK-418 5 mg</title>
            <description>TAK-418 5 mg, capsule, orally, once on Day 1.</description>
          </group>
          <group group_id="O3">
            <title>Cohort 2: TAK-418 15 mg</title>
            <description>TAK-418 15 mg, capsule, orally, once on Day 1.</description>
          </group>
          <group group_id="O4">
            <title>Cohort 3A: TAK-418 30 mg Fasted</title>
            <description>TAK-418 30 mg, capsule, in fasted state, orally, once on Day 1.</description>
          </group>
          <group group_id="O5">
            <title>Cohort 3B: TAK-418 30 mg Fed</title>
            <description>TAK-418 30 mg, capsule, in fed state, orally, once on Day 1.</description>
          </group>
          <group group_id="O6">
            <title>Cohort 4: TAK-418 40 mg</title>
            <description>TAK-418 40 mg, capsule, orally, once on Day 1.</description>
          </group>
          <group group_id="O7">
            <title>Cohort 5: TAK-418 60 mg</title>
            <description>TAK-418 60 mg, capsule, orally, once on Day 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post Dose</title>
          <population>The safety analysis set included all randomized participants who received at least 1 dose of study drug.</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="6"/>
                <count group_id="O5" value="5"/>
                <count group_id="O6" value="6"/>
                <count group_id="O7" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="0"/>
                    <measurement group_id="O7" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose</title>
        <time_frame>Baseline Up to day 184</time_frame>
        <population>The safety analysis set included all randomized participants who received at least 1 dose of study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohorts 1-5: Placebo</title>
            <description>TAK-418 placebo-matching, capsule, orally, once on Day 1.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 1: TAK-418 5 mg</title>
            <description>TAK-418 5 mg, capsule, orally, once on Day 1.</description>
          </group>
          <group group_id="O3">
            <title>Cohort 2: TAK-418 15 mg</title>
            <description>TAK-418 15 mg, capsule, orally, once on Day 1.</description>
          </group>
          <group group_id="O4">
            <title>Cohort 3A: TAK-418 30 mg Fasted</title>
            <description>TAK-418 30 mg, capsule, in fasted state, orally, once on Day 1.</description>
          </group>
          <group group_id="O5">
            <title>Cohort 3B: TAK-418 30 mg Fed</title>
            <description>TAK-418 30 mg, capsule, in fed state, orally, once on Day 1.</description>
          </group>
          <group group_id="O6">
            <title>Cohort 4: TAK-418 40 mg</title>
            <description>TAK-418 40 mg, capsule, orally, once on Day 1.</description>
          </group>
          <group group_id="O7">
            <title>Cohort 5: TAK-418 60 mg</title>
            <description>TAK-418 60 mg, capsule, orally, once on Day 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose</title>
          <population>The safety analysis set included all randomized participants who received at least 1 dose of study drug.</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="6"/>
                <count group_id="O5" value="5"/>
                <count group_id="O6" value="6"/>
                <count group_id="O7" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Diastolic blood pressure less than (&lt;) 50 mmHg</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="0"/>
                    <measurement group_id="O7" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Systolic blood pressure &lt; 85 mmHg</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="1"/>
                    <measurement group_id="O6" value="0"/>
                    <measurement group_id="O7" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Temperature &lt; 35.6 degrees celsius (°C)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="1"/>
                    <measurement group_id="O5" value="1"/>
                    <measurement group_id="O6" value="1"/>
                    <measurement group_id="O7" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Temperature greater than (&gt;) 37.7 (°C)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="0"/>
                    <measurement group_id="O7" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants Who Meet the Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Parameters at Least Once Post Dose</title>
        <time_frame>Baseline Up to Day 14</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Cohorts 1-5: Placebo</title>
            <description>TAK-418 placebo-matching, capsule, orally, once on Day 1.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 1: TAK-418 5 mg</title>
            <description>TAK-418 5 mg, capsule, orally, once on Day 1.</description>
          </group>
          <group group_id="O3">
            <title>Cohort 2: TAK-418 15 mg</title>
            <description>TAK-418 15 mg, capsule, orally, once on Day 1.</description>
          </group>
          <group group_id="O4">
            <title>Cohort 3A: TAK-418 30 mg Fasted</title>
            <description>TAK-418 30 mg, capsule, in fasted state, orally, once on Day 1.</description>
          </group>
          <group group_id="O5">
            <title>Cohort 3B: TAK-418 30 mg Fed</title>
            <description>TAK-418 30 mg, capsule, in fed state, orally, once on Day 1.</description>
          </group>
          <group group_id="O6">
            <title>Cohort 4: TAK-418 40 mg</title>
            <description>TAK-418 40 mg, capsule, orally, once on Day 1.</description>
          </group>
          <group group_id="O7">
            <title>Cohort 5: TAK-418 60 mg</title>
            <description>TAK-418 60 mg, capsule, orally, once on Day 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Who Meet the Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Parameters at Least Once Post Dose</title>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="6"/>
                <count group_id="O5" value="5"/>
                <count group_id="O6" value="6"/>
                <count group_id="O7" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>ECG ventricular rate(Beats/ minute)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="0"/>
                    <measurement group_id="O7" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>QT interval (Milliseconds)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="0"/>
                    <measurement group_id="O7" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration of TAK-418F (TAK-418 Free Base)</title>
        <time_frame>Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose</time_frame>
        <population>The pharmacokinetic analysis set included all participants who received at least 1 dose of study drug and had at least one measurable plasma concentration or amount of drug in urine for TAK-418-F.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1: TAK-418 5 mg</title>
            <description>TAK-418 5 mg, capsule, orally, once on Day 1.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2: TAK-418 15 mg</title>
            <description>TAK-418 15 mg, capsule, orally, once on Day 1.</description>
          </group>
          <group group_id="O3">
            <title>Cohort 3A: TAK-418 30 mg Fasted</title>
            <description>TAK-418 30 mg, capsule, in fasted state, orally, once on Day 1.</description>
          </group>
          <group group_id="O4">
            <title>Cohort 3B: TAK-418 30 mg Fed</title>
            <description>TAK-418 30 mg, capsule, in fed state, orally, once on Day 1.</description>
          </group>
          <group group_id="O5">
            <title>Cohort 4: TAK-418 40 mg</title>
            <description>TAK-418 40 mg, capsule, orally, once on Day 1.</description>
          </group>
          <group group_id="O6">
            <title>Cohort 5: TAK-418 60 mg</title>
            <description>TAK-418 60 mg, capsule, orally, once on Day 1.</description>
          </group>
        </group_list>
        <measure>
          <title>AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration of TAK-418F (TAK-418 Free Base)</title>
          <population>The pharmacokinetic analysis set included all participants who received at least 1 dose of study drug and had at least one measurable plasma concentration or amount of drug in urine for TAK-418-F.</population>
          <units>hour nanogram per milliliter (h*ng/mL)</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="5"/>
                <count group_id="O5" value="6"/>
                <count group_id="O6" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="77.3" spread="47.1"/>
                    <measurement group_id="O2" value="290.4" spread="21.8"/>
                    <measurement group_id="O3" value="649.4" spread="8.5"/>
                    <measurement group_id="O4" value="616.2" spread="23.1"/>
                    <measurement group_id="O5" value="674.1" spread="27.0"/>
                    <measurement group_id="O6" value="1576.3" spread="33.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>A linear mixed effect model on the natural log-transformed parameters was performed with a fixed effect for regimen and random effect for participant. The least squares(LS) means and difference of least squares (LS) means for the log-transformed parameters were exponentiated to obtain the point estimates (Geometric LS means) of the food effect and 90% confidence intervals (CIs).</non_inferiority_desc>
            <param_type>Least Squares (LS) Mean Difference</param_type>
            <param_value>0.951</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.823</ci_lower_limit>
            <ci_upper_limit>1.099</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
              <group_id>O5</group_id>
              <group_id>O6</group_id>
            </group_id_list>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>A linear regression model (power model), log (ln) (parameter) equal to (=) intercept plus (+) slope*ln (dose), was fit to describe the relationship between each parameter and the corresponding dose levels. Dose Proportionality was declared if the 90% CI of the slope lied entirely within the critical region as defined by 1 - ln(0.8) per (/)l n(r) to 1 + ln(1.25)/ln(r), where r was the ratio of the highest and lowest dose in the study.</non_inferiority_desc>
            <param_type>Slope</param_type>
            <param_value>1.14</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.04</ci_lower_limit>
            <ci_upper_limit>1.25</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-418F</title>
        <time_frame>Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose</time_frame>
        <population>The pharmacokinetic analysis set included all participants who received at least 1 dose of study drug and had at least one measurable plasma concentration or amount of drug in urine for TAK-418-F.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1: TAK-418 5 mg</title>
            <description>TAK-418 5 mg, capsule, orally, once on Day 1.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2: TAK-418 15 mg</title>
            <description>TAK-418 15 mg, capsule, orally, once on Day 1.</description>
          </group>
          <group group_id="O3">
            <title>Cohort 3A: TAK-418 30 mg Fasted</title>
            <description>TAK-418 30 mg, capsule, in fasted state, orally, once on Day 1.</description>
          </group>
          <group group_id="O4">
            <title>Cohort 3B: TAK-418 30 mg Fed</title>
            <description>TAK-418 30 mg, capsule, in fed state, orally, once on Day 1.</description>
          </group>
          <group group_id="O5">
            <title>Cohort 4: TAK-418 40 mg</title>
            <description>TAK-418 40 mg, capsule, orally, once on Day 1.</description>
          </group>
          <group group_id="O6">
            <title>Cohort 5: TAK-418 60 mg</title>
            <description>TAK-418 60 mg, capsule, orally, once on Day 1.</description>
          </group>
        </group_list>
        <measure>
          <title>AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-418F</title>
          <population>The pharmacokinetic analysis set included all participants who received at least 1 dose of study drug and had at least one measurable plasma concentration or amount of drug in urine for TAK-418-F.</population>
          <units>h*ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="5"/>
                <count group_id="O5" value="6"/>
                <count group_id="O6" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="84.9" spread="47.4"/>
                    <measurement group_id="O2" value="296.3" spread="22.1"/>
                    <measurement group_id="O3" value="659.6" spread="8.0"/>
                    <measurement group_id="O4" value="626.0" spread="22.7"/>
                    <measurement group_id="O5" value="681.0" spread="26.9"/>
                    <measurement group_id="O6" value="1519.9" spread="33.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>Bioequivalence interval of 627.51 to 659.59</non_inferiority_desc>
            <param_type>LS Mean Difference</param_type>
            <param_value>0.951</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.825</ci_lower_limit>
            <ci_upper_limit>1.097</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
              <group_id>O5</group_id>
              <group_id>O6</group_id>
            </group_id_list>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>A linear regression model (power model), ln (parameter) = intercept + slope*ln (dose), was fit to describe the relationship between each parameter and the corresponding dose levels. Dose Proportionality was declared if the 90% CI of the slope lied entirely within the critical region as defined by 1 - ln (0.8)/l n(r) to 1 + ln (1.25)/ln(r), where r was the ratio of the highest and lowest dose in the study.</non_inferiority_desc>
            <param_type>Slope</param_type>
            <param_value>1.11</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.00</ci_lower_limit>
            <ci_upper_limit>1.22</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cmax: Maximum Observed Plasma Concentration for TAK-418F</title>
        <time_frame>Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose</time_frame>
        <population>The pharmacokinetic analysis set included all participants who received at least 1 dose of study drug and had at least one measurable plasma concentration or amount of drug in urine for TAK-418-F.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1: TAK-418 5 mg</title>
            <description>TAK-418 5 mg, capsule, orally, once on Day 1.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2: TAK-418 15 mg</title>
            <description>TAK-418 15 mg, capsule, orally, once on Day 1.</description>
          </group>
          <group group_id="O3">
            <title>Cohort 3A: TAK-418 30 mg Fasted</title>
            <description>TAK-418 30 mg, capsule, in fasted state, orally, once on Day 1.</description>
          </group>
          <group group_id="O4">
            <title>Cohort 3B: TAK-418 30 mg Fed</title>
            <description>TAK-418 30 mg, capsule, in fed state, orally, once on Day 1.</description>
          </group>
          <group group_id="O5">
            <title>Cohort 4: TAK-418 40 mg</title>
            <description>TAK-418 40 mg, capsule, orally, once on Day 1.</description>
          </group>
          <group group_id="O6">
            <title>Cohort 5: TAK-418 60 mg</title>
            <description>TAK-418 60 mg, capsule, orally, once on Day 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Cmax: Maximum Observed Plasma Concentration for TAK-418F</title>
          <population>The pharmacokinetic analysis set included all participants who received at least 1 dose of study drug and had at least one measurable plasma concentration or amount of drug in urine for TAK-418-F.</population>
          <units>nanogram per millilitre (ng/mL)</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="5"/>
                <count group_id="O5" value="6"/>
                <count group_id="O6" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="21.54" spread="35.9"/>
                    <measurement group_id="O2" value="61.90" spread="26.6"/>
                    <measurement group_id="O3" value="163.64" spread="20.9"/>
                    <measurement group_id="O4" value="94.93" spread="33.8"/>
                    <measurement group_id="O5" value="155.32" spread="34.3"/>
                    <measurement group_id="O6" value="321.52" spread="14.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>A linear mixed effect model on the natural log-transformed parameters was performed with a fixed effect for regimen and random effect for participant. The LS means and difference of LS means for the log-transformed parameters were exponentiated to obtain the point estimates (Geometric LS means) of the food effect and 90% confidence intervals CIs.</non_inferiority_desc>
            <param_type>LS Mean Difference</param_type>
            <param_value>0.580</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.431</ci_lower_limit>
            <ci_upper_limit>0.781</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
              <group_id>O5</group_id>
              <group_id>O6</group_id>
            </group_id_list>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>A linear regression model (power model), ln (parameter) = intercept + slope*ln (dose), was fit to describe the relationship between each parameter and the corresponding dose levels. Dose Proportionality was declared if the 90% CI of the slope lied entirely within the critical region as defined by 1 - ln (0.8)/l n(r) to 1 + ln (1.25)/ln(r), where r was the ratio of the highest and lowest dose in the study.</non_inferiority_desc>
            <param_type>Slope</param_type>
            <param_value>1.06</param_value>
            <ci_percent>90</ci_percent>
            <ci_lower_limit>0.96</ci_lower_limit>
            <ci_upper_limit>1.17</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-418F</title>
        <description>The pharmacokinetic analysis set included all participants who received at least 1 dose of study drug and had at least one measurable plasma concentration or amount of drug in urine for TAK-418-F.</description>
        <time_frame>Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1: TAK-418 5 mg</title>
            <description>TAK-418 5 mg, capsule, orally, once on Day 1.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2: TAK-418 15 mg</title>
            <description>TAK-418 15 mg, capsule, orally, once on Day 1.</description>
          </group>
          <group group_id="O3">
            <title>Cohort 3A: TAK-418 30 mg Fasted</title>
            <description>TAK-418 30 mg, capsule, in fasted state, orally, once on Day 1.</description>
          </group>
          <group group_id="O4">
            <title>Cohort 3B: TAK-418 30 mg Fed</title>
            <description>TAK-418 30 mg, capsule, in fed state, orally, once on Day 1.</description>
          </group>
          <group group_id="O5">
            <title>Cohort 4: TAK-418 40 mg</title>
            <description>TAK-418 40 mg, capsule, orally, once on Day 1.</description>
          </group>
          <group group_id="O6">
            <title>Cohort 5: TAK-418 60 mg</title>
            <description>TAK-418 60 mg, capsule, orally, once on Day 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-418F</title>
          <description>The pharmacokinetic analysis set included all participants who received at least 1 dose of study drug and had at least one measurable plasma concentration or amount of drug in urine for TAK-418-F.</description>
          <units>hour</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="5"/>
                <count group_id="O5" value="6"/>
                <count group_id="O6" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.000" lower_limit="0.98" upper_limit="1.02"/>
                    <measurement group_id="O2" value="1.000" lower_limit="1.00" upper_limit="2.00"/>
                    <measurement group_id="O3" value="1.000" lower_limit="0.50" upper_limit="1.00"/>
                    <measurement group_id="O4" value="3.000" lower_limit="1.50" upper_limit="3.02"/>
                    <measurement group_id="O5" value="1.250" lower_limit="1.00" upper_limit="1.52"/>
                    <measurement group_id="O6" value="1.000" lower_limit="1.00" upper_limit="1.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Treatment-emergent adverse events are adverse events that started after the first dose of the study drug up to Day 184</time_frame>
      <desc>At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.</desc>
      <group_list>
        <group group_id="E1">
          <title>Cohorts 1-5: Placebo</title>
          <description>TAK-418 placebo-matching, capsule, orally, once on Day 1.</description>
        </group>
        <group group_id="E2">
          <title>Cohort 1: TAK-418 5 mg</title>
          <description>TAK-418 5 mg, capsule, orally, once on Day 1.</description>
        </group>
        <group group_id="E3">
          <title>Cohort 2: TAK-418 15 mg</title>
          <description>TAK-418 15 mg, capsule, orally, once on Day 1.</description>
        </group>
        <group group_id="E4">
          <title>Cohort 3A: TAK-418 30 mg Fasted</title>
          <description>TAK-418 30 mg, capsule, in fasted state, orally, once on Day 1.</description>
        </group>
        <group group_id="E5">
          <title>Cohort 3B: TAK-418 30 mg Fed</title>
          <description>TAK-418 30 mg, capsule, in fed state, orally, once on Day 1.</description>
        </group>
        <group group_id="E6">
          <title>Cohort 4: TAK-418 40 mg</title>
          <description>TAK-418 40 mg, capsule, orally, once on Day 1.</description>
        </group>
        <group group_id="E7">
          <title>Cohort 5: TAK-418 60 mg</title>
          <description>TAK-418 60 mg, capsule, orally, once on Day 1.</description>
        </group>
      </group_list>
      <serious_events>
        <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="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA (21.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E6" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="3" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Eye irritation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Dental caries</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="2" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Groin pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Limb discomfort</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Testicular pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Erectile dysfunction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Dermatitis contact</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Night sweats</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
              </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>Research Organization shall not publish any articles or papers nor make any presentations, nor assist any other person in publishing any articles or papers or in making any presentations relating or referring to the Study or any results, data or insights from or any data, information or materials obtained or generated in the performance of its obligations without the prior written consent of Takeda, which consent may be granted or withheld in Takeda's sole discretion .</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Medical Director</name_or_title>
      <organization>Takeda</organization>
      <phone>+1-877-825-3327</phone>
      <email>trialdisclosures@takeda.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03228433
org study id: TAK-418-1001
secondary id: U1111-1195-7777
nct id: NCT03228433
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to evaluate the safety and tolerability of TAK-418 following
      single oral doses in healthy participants.
The drug being tested in this study is called TAK-418. TAK-418 is being tested in healthy
      participants in order to evaluate the safety, tolerability, and pharmacokinetics (PK) of
      single oral doses.

      The study will enroll approximately 40 healthy participants. The study consists of equally
      divided 5 sequential cohorts of 8 participants each. In each of the following cohorts, 6
      participants will be randomized to receive TAK-418 and 2 participants will receive matching
      placebo-which will remain undisclosed to the participant and study doctor during the study
      (unless there is an urgent medical need):

        -  Cohort 1: TAK-418 5 mg

        -  Cohort 2: TAK-418 15 mg

        -  Cohort 3: TAK-418 30 mg Fasted + TAK-418 30 mg Fed

        -  Cohort 4: TAK-418 40 mg

        -  Cohort 5: TAK-418 60 mg

      All participants will be asked to take TAK-418 or placebo-matching capsule once on Day 1 in
      each cohort. A washout period of 28-days will be maintained between the doses in Cohort 3.

      This single center trial will be conducted in the United States. Participants in this study
      will be assigned to one of 5 possible dose cohorts. Male participants will return for
      additional outpatient visits on Days 91 and 93 (+/- 7 days) and may return for outpatient
      visits on Days 182 and 184 (+/- 7 days) (depending on results from the Day 93 Visit).
allocation: Randomized
intervention model: Sequential Assignment
primary purpose: Other
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)
time frame: Baseline Up to Day 184
measure: Number of Participants Who Discontinued Due to an Adverse Event (AE)
time frame: Baseline Up to Day 184
measure: Number of Participants Who Meet the Markedly Abnormal Criteria for Neurological Assessment Measurements at Least Once Post Dose
time frame: Baseline Up to Day 184
measure: Number of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post Dose
time frame: Baseline Up to Day 184
measure: Number of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose
time frame: Baseline Up to day 184
measure: Number of Participants Who Meet the Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Parameters at Least Once Post Dose
time frame: Baseline Up to Day 14
measure: AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration of TAK-418F (TAK-418 Free Base)
time frame: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose
measure: AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-418F
time frame: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose
measure: Cmax: Maximum Observed Plasma Concentration for TAK-418F
time frame: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose
measure: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-418F
time frame: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose
description: The pharmacokinetic analysis set included all participants who received at least 1 dose of study drug and had at least one measurable plasma concentration or amount of drug in urine for TAK-418-F.
arm group label: Cohort 1: TAK-418 5 mg
arm group type: Experimental
description: TAK-418 5 milligram (mg), capsule, orally, once on Day 1.
arm group label: Cohort 2: TAK-418 15 mg
arm group type: Experimental
description: TAK-418 15 mg, capsule, orally, once on Day 1. Actual dose of TAK-418 may vary based on safety, tolerability and PK data from previous Cohorts.
arm group label: Cohort 3: TAK-418 30 mg Fasted + TAK-418 30 mg Fed
arm group type: Experimental
description: TAK-418 30 mg, capsule, in fasted state, orally, once on Day 1, followed by a 28-day washout period, further followed by TAK-418 30 mg, capsule, in fed state, orally, once on Day 1. Actual dose of TAK-418 may vary based on safety, tolerability and PK data from previous Cohorts.
arm group label: Cohort 4: TAK-418 40 mg
arm group type: Experimental
description: TAK-418 40 mg, capsule, orally, once on Day 1. Actual dose of TAK-418 may vary based on safety, tolerability and PK data from previous Cohorts.
arm group label: Cohort 5: TAK-418 60 mg
arm group type: Experimental
description: TAK-418 60 mg, capsule, orally, once on Day 1. Actual dose of TAK-418 may vary based on safety, tolerability and PK data from previous Cohorts.
arm group label: Cohorts 1-5: Placebo
arm group type: Placebo Comparator
description: TAK-418 placebo-matching, capsule, orally, once on Day 1.
intervention type: Drug
intervention name: TAK-418
description: TAK-418 Capsule.
arm group label: Cohort 1: TAK-418 5 mg
arm group label: Cohort 2: TAK-418 15 mg
arm group label: Cohort 3: TAK-418 30 mg Fasted + TAK-418 30 mg Fed
arm group label: Cohort 4: TAK-418 40 mg
arm group label: Cohort 5: TAK-418 60 mg
intervention type: Drug
intervention name: TAK-418 Placebo
description: TAK-418 placebo-matching capsules.
arm group label: Cohorts 1-5: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Medical Director
role: Study Director
affiliation: Takeda
facility: 
country: United States
responsible party type: Sponsor
sharing ipd: Yes
ipd description: Takeda makes patient-level, de-identified data sets and associated documents available after applicable marketing approvals and commercial availability have been received, an opportunity for the primary publication of the research has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com/Approach for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 