<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/NCT04461483</url>
  </required_header>
  <id_info>
    <org_study_id>TAK-935-1004</org_study_id>
    <secondary_id>U1111-1252-8555</secondary_id>
    <secondary_id>JapicCTI-205349</secondary_id>
    <nct_id>NCT04461483</nct_id>
  </id_info>
  <brief_title>A Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Single Ascending Dose and Multiple Doses With Titration of TAK-935 in Healthy Japanese Participants</brief_title>
  <official_title>A Randomized, Double-blind, Placebo-Controlled, Phase 1 Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Single Ascending Dose and Multiple Doses With Titration of TAK-935 in Healthy Japanese 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>No</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, tolerability, pharmacokinetics, and&#xD;
      pharmacodynamics of TAK-935 with single ascending doses (Part 1) and multiple doses with&#xD;
      titration (Part 2).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The drug being tested in this study is called TAK-935 tablet. TAK-935 tablet is being tested&#xD;
      in Japanese healthy adult men. This study will evaluate the safety, tolerability,&#xD;
      pharmacokinetics, and pharmacodynamics of TAK-935 with single ascending doses (Part 1) and&#xD;
      multiple doses with titration (Part 2).&#xD;
&#xD;
      The study will enroll up to 33 participants in total (Part 1 + 2). In Part 1, participants&#xD;
      will be randomly assigned (by chance, like flipping a coin) to one of these treatment&#xD;
      cohorts/groups;&#xD;
&#xD;
        -  Cohort 1: Single dose of TAK-935 at 200 mg or placebo (fasted)&#xD;
&#xD;
        -  Cohort 2: Single dose of TAK-935 at 600 mg or placebo (fasted)&#xD;
&#xD;
        -  Cohort 3: Single dose of TAK-935 at 1200 mg or placebo (fasted)&#xD;
&#xD;
      In Part 2, participants will be randomly assigned to one of these treatment groups;&#xD;
&#xD;
      - Cohort 4: Multiple doses with titration of TAK-935 or placebo at 100 mg twice daily (BID)&#xD;
      from Day 1 to Day 7, 200 mg BID from Day 8 to Day 14 and 300 mg BID from Day 15 to Day 21&#xD;
      (fasted).&#xD;
&#xD;
      This single-center trial will be conducted in Japan. The overall time to participate in this&#xD;
      study is approximately 36 days for Part 1 and 63 days for Part 2. Participants will be&#xD;
      hospitalized for 5 days in Part 1 and 26 days in Part 2.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 13, 2020</start_date>
  <completion_date type="Actual">November 14, 2020</completion_date>
  <primary_completion_date type="Actual">November 14, 2020</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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Parts 1 and 2: Percentage of Participants With at Least One Treatment-emergent Adverse Event (TEAE)</measure>
    <time_frame>Part 1: Baseline up to Day 8; Part 2: Baseline up to Day 35</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-935</measure>
    <time_frame>Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 2, Cmax: Maximum Observed Plasma Concentration for TAK-935</measure>
    <time_frame>Days 7, 14, and 21 pre-dose and at multiple time points (up to 12 hours) post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for TAK-935</measure>
    <time_frame>Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 1, AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Time of Infinity for TAK-935</measure>
    <time_frame>Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 1, AUC(0-24): Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours Post-dose for TAK-935</measure>
    <time_frame>Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 2, AUCtau,ss: Area Under the Plasma Concentration-time Curve During the Dosing Interval at Steady State for TAK-935</measure>
    <time_frame>Days 7, 14, and 21 pre-dose and at multiple time points (up to 12 hours) post-dose</time_frame>
  </secondary_outcome>
  <number_of_arms>8</number_of_arms>
  <enrollment type="Actual">33</enrollment>
  <condition>Healthy Volunteer</condition>
  <arm_group>
    <arm_group_label>Part 1, Cohort 1; TAK-935 200 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Part 1, Cohort 1; TAK-935 200 mg, tablets, orally once on Days 1 in fasted state.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 1, Cohort 2; TAK-935 600 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Part 1, Cohort 2; TAK-935 600 mg, tablets, orally once on Days 1 in fasted state.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 1, Cohort 3; TAK-935 1200 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Part 1, Cohort 3; TAK-935 1200 mg, tablets, orally once on Days 1 in fasted state.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 1, Cohort 1-3; Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Part 1, Cohort 1-3; TAK-935 placebo-matching tablets, orally once on Days 1 in fasted state.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2, Cohort 4: TAK-935 100 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Part 2, Cohort 4: TAK-935 100 mg, tablets, orally twice on Days 1-7 in fasted state with multiple doses with titration.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2, Cohort 4: TAK-935 200 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Part 2, Cohort 4: TAK-935 200 mg, tablets, orally twice on Days 8-14 in fasted state with multiple doses with titration.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2, Cohort 4: TAK-935 300 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Part 2, Cohort 4: TAK-935 300 mg, tablets, orally twice on Days 15-21 in fasted state with multiple doses with titration.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2, Cohort 4: Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Part 2, Cohort 4: TAK-935 placebo-matching tablets, orally twice on Days 1-21 in fasted state.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TAK-935</intervention_name>
    <description>TAK-935 Tablets</description>
    <arm_group_label>Part 1, Cohort 1; TAK-935 200 mg</arm_group_label>
    <arm_group_label>Part 1, Cohort 2; TAK-935 600 mg</arm_group_label>
    <arm_group_label>Part 1, Cohort 3; TAK-935 1200 mg</arm_group_label>
    <arm_group_label>Part 2, Cohort 4: TAK-935 100 mg</arm_group_label>
    <arm_group_label>Part 2, Cohort 4: TAK-935 200 mg</arm_group_label>
    <arm_group_label>Part 2, Cohort 4: TAK-935 300 mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>TAK-935 placebo-matching tablets</description>
    <arm_group_label>Part 1, Cohort 1-3; Placebo</arm_group_label>
    <arm_group_label>Part 2, Cohort 4: Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. The participant must understand the study procedures and agree to participate by&#xD;
             providing written informed consent.&#xD;
&#xD;
          2. The participant must be willing and able to comply with all study procedures and&#xD;
             restrictions.&#xD;
&#xD;
          3. The participant must be a Japanese healthy adult male or female, aged 20 to 55 years,&#xD;
             inclusive, at the time of informed consent.&#xD;
&#xD;
          4. The participant must have a body mass index (BMI) &gt;=18.5 and =&lt;25.0 kg/m^2 at the&#xD;
             Screening Visit.&#xD;
&#xD;
          5. The participant must be a current nonsmoker who has not used tobacco- or&#xD;
             nicotine-containing products (eg, nicotine patch) for at least 6 months prior to the&#xD;
             first dose of study drug or first invasive procedure.&#xD;
&#xD;
          6. The participant must be judged to be in good health by the investigator, based on&#xD;
             clinical evaluations including laboratory safety tests, medical history, physical&#xD;
             examination, 12-lead electrocardiogram, and vital sign measurements performed at the&#xD;
             Screening Visit and prior to the first dose of study drug.&#xD;
&#xD;
          7. The participant must meet the following birth control requirements:&#xD;
&#xD;
               -  Is a male participant who is sterile or agrees to use an appropriate method of&#xD;
                  contraception, including a condom with spermicidal cream or jelly, from the first&#xD;
                  dose of study drug until 90 days after the last dose of study drug. No&#xD;
                  restrictions are required for a vasectomized male participant provided the&#xD;
                  participant is at least 1-year postbilateral vasectomy procedure prior to the&#xD;
                  first dose of study drug. A male participant whose vasectomy procedure was&#xD;
                  performed less than 1 year prior to the first dose of study drug must follow the&#xD;
                  same restrictions as a nonvasectomized man. Appropriate documentation of surgical&#xD;
                  procedure should be provided.&#xD;
&#xD;
               -  Is a male participant who agrees to not donate sperm from the first dose of study&#xD;
                  drug until 90 days after the last dose of study drug.&#xD;
&#xD;
               -  Is a female participant of nonchildbearing potential, defined by at least 1 of&#xD;
                  the following criteria:&#xD;
&#xD;
                    1. Postmenopausal (defined as 12 months of spontaneous amenorrhea in females&#xD;
                       aged &gt;45 years or &gt;=6 months of spontaneous amenorrhea in females aged &gt;45&#xD;
                       years with serum follicle-stimulating hormone [FSH] levels &gt;40 mIU/mL).&#xD;
                       Appropriate documentation of follicle-stimulating hormone levels should be&#xD;
                       required.&#xD;
&#xD;
                    2. Hysterectomy and/or bilateral oophorectomy with appropriate documentation of&#xD;
                       surgical procedure.&#xD;
&#xD;
                    3. Had a tubal ligation with appropriate documentation of surgical procedure.&#xD;
&#xD;
                    4. Congenital conditions such as uterine aplasia etc.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Has a history of clinically significant endocrine, gastrointestinal (including&#xD;
             motility disorder and intestinal obstruction), cardiovascular (including arrhythmia),&#xD;
             hematological, hepatic, immunological, renal, respiratory, genitourinary, major&#xD;
             neurological (including stroke, epileptic seizure), or degenerative ophthalmological&#xD;
             abnormalities or diseases&#xD;
&#xD;
          2. Has participated in another investigational trial within 4 weeks or 5 half-lives&#xD;
             (whichever is longer) before the pretrial visit (Screening). The 4-week or 5&#xD;
             half-lives window will be derived from the date of the last trial procedure and/or AE&#xD;
             related to the trial procedure in the previous trial to the pretrial/Screening Visit&#xD;
             of the current trial.&#xD;
&#xD;
          3. Is an employee or immediate family member (eg, spouse, parent, child, sibling) of the&#xD;
             sponsor.&#xD;
&#xD;
          4. Has a history of cancer (malignancy).&#xD;
&#xD;
          5. Has any lifetime history of a suicide attempt, or have suicidal ideation or, any&#xD;
             suicidal behavior within 12 months, or who are at significant risk to commit suicide,&#xD;
             as judged by the investigator using the Columbia Suicide Severity Rating Scale&#xD;
             (C-SSRS) or is clinically judged by the investigator to be at risk for suicide.&#xD;
&#xD;
          6. Has a history of significant multiple and/or severe allergies (eg, food, drug, latex&#xD;
             allergy) or has had an anaphylactic reaction or significant intolerability to&#xD;
             prescription or nonprescription drugs or food.&#xD;
&#xD;
          7. Has a positive alcohol or drug screen.&#xD;
&#xD;
          8. Had major surgery, donated or lost whole blood prior to the start of study drug&#xD;
             administration as any of below:&#xD;
&#xD;
             For both male and female participants, &gt;=200 mL within 4 weeks (28 days) For male&#xD;
             participants, &gt;=400 mL within 12 weeks (84 days), &gt;=800 mL in total within 52 weeks&#xD;
             (364 days) For female participants, &gt;=400 mL within 16 weeks (112 days). &gt;=400 mL in&#xD;
             total within 52 weeks (364 days)&#xD;
&#xD;
          9. Had gastrointestinal surgery that could impact the absorption of study drug.&#xD;
&#xD;
         10. Has a history of a major psychiatric disorder as diagnosed utilizing Diagnostic and&#xD;
             Statistical Manual of Mental Disorders, 5th Edition criteria.&#xD;
&#xD;
         11. Has a known hypersensitivity to any component of the formulation of TAK-935 or related&#xD;
             compounds.&#xD;
&#xD;
         12. Is unable to refrain from or anticipates the use of any medication, including&#xD;
             prescription and nonprescription drugs or herbal remedies, beginning approximately 7&#xD;
             days before administration of the initial dose of study drug, throughout the trial&#xD;
             (including washout intervals between trial periods), until the Follow-up Visit.&#xD;
&#xD;
         13. Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol&#xD;
             abuse within 1 year prior to the Screening visit or is unwilling to agree to abstain&#xD;
             from alcohol and drugs throughout the study.&#xD;
&#xD;
         14. Consumes excessive amounts, defined as greater than 6 servings (1 serving is&#xD;
             approximately equivalent to 120 mg of caffeine) of coffee, tea, cola, energy drinks,&#xD;
             or other caffeinated beverages per day.&#xD;
&#xD;
         15. Has a substance abuse disorder.&#xD;
&#xD;
         16. Has a QTcF &gt;450 msec confirmed with one repeat testing, at the Screening Visit.&#xD;
&#xD;
         17. Had abnormal Screening or Day -1 laboratory values that suggested a clinically&#xD;
             significant underlying disease or participant with the following laboratory&#xD;
             abnormalities: ALT and/or AST &gt;1.5 time ULN.&#xD;
&#xD;
         18. Has tested positive for hepatitis B virus surface antigen (HBsAg), hepatitis C virus&#xD;
             (HCV) antibody, HIV antibody/antigen, or serologic reactions for syphilis at&#xD;
             Screening.&#xD;
&#xD;
         19. In the opinion of the investigator, is unlikely to comply with the protocol or is&#xD;
             unsuitable for any other reason.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Study Director</last_name>
    <role>Study Director</role>
    <affiliation>Takeda</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Clinical Research Hospital Tokyo</name>
      <address>
        <city>Shinjuku-ku</city>
        <state>Tokyo</state>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Japan</country>
  </location_countries>
  <verification_date>November 2020</verification_date>
  <study_first_submitted>July 3, 2020</study_first_submitted>
  <study_first_submitted_qc>July 3, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 8, 2020</study_first_posted>
  <results_first_submitted>November 10, 2021</results_first_submitted>
  <results_first_submitted_qc>November 10, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">January 11, 2022</results_first_posted>
  <last_update_submitted>November 10, 2021</last_update_submitted>
  <last_update_submitted_qc>November 10, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">January 11, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_access_criteria>IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.</ipd_access_criteria>
    <ipd_url>https://vivli.org/ourmember/takeda/</ipd_url>
  </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 2, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/83/NCT04461483/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>November 20, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/83/NCT04461483/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants took part in the study at 1 investigative site in Japan from 13 August 2020 to 14 November 2020.</recruitment_details>
      <pre_assignment_details>Healthy Japanese participants were enrolled in the study into two parts: Single Ascending Dose (SAD) (Part 1) and Multiple Dose (MD) titration (Part 2) to receive TAK-935 tablets or TAK-935 placebo-matching tablets.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Part 1, SAD, Cohorts 1 to 3: Placebo</title>
          <description>TAK-935 placebo-matching tablet, orally, once on Day 1 in fasted state.</description>
        </group>
        <group group_id="P2">
          <title>Part 1, SAD, Cohort 1: TAK-935 200 mg</title>
          <description>TAK-935 200 milligram (mg), tablet, orally, once on Day 1 in fasted state.</description>
        </group>
        <group group_id="P3">
          <title>Part 1, SAD, Cohort 2: TAK-935 600 mg</title>
          <description>TAK-935 600 mg, tablet, orally, once on Day 1 in fasted state.</description>
        </group>
        <group group_id="P4">
          <title>Part 1, SAD, Cohort 3: TAK-935 1200 mg</title>
          <description>TAK-935 1200 mg, tablet, orally, once on Day 1 in fasted state.</description>
        </group>
        <group group_id="P5">
          <title>Part 2, MD, Cohort 4: Placebo</title>
          <description>TAK-935 placebo-matching tablets, orally, twice daily on Days 1 to 21 in fasted state.</description>
        </group>
        <group group_id="P6">
          <title>Part 2, MD, Cohort 4: TAK-935</title>
          <description>TAK-935 100 mg, tablets, orally, twice daily on Days 1 to 7, then up-titrated to TAK-935 200 mg, tablets, orally, twice daily, on Days 8 to 14, further up-titrated to TAK-935 300 mg, tablets, orally, twice daily on Days 15 to 21 as multiple doses with titration in the fasted state.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Part 1 (Day 1)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="6"/>
                <participants group_id="P4" count="6"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="6"/>
                <participants group_id="P4" count="6"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</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="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Part 2 (Day 1 to 21)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</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="0"/>
                <participants group_id="P5" count="3"/>
                <participants group_id="P6" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</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="0"/>
                <participants group_id="P5" count="3"/>
                <participants group_id="P6" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</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="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The safety analysis set included all participants who received at least 1 dose of study drug.</population>
      <group_list>
        <group group_id="B1">
          <title>Part 1, SAD, Cohorts 1 to 3: Placebo</title>
          <description>TAK-935 placebo-matching tablet, orally, once on Day 1 in fasted state.</description>
        </group>
        <group group_id="B2">
          <title>Part 1, SAD, Cohort 1: TAK-935 200 mg</title>
          <description>TAK-935 200 mg, tablet, orally, once on Day 1 in fasted state.</description>
        </group>
        <group group_id="B3">
          <title>Part 1, SAD, Cohort 2: TAK-935 600 mg</title>
          <description>TAK-935 600 mg, tablet, orally, once on Day 1 in fasted state.</description>
        </group>
        <group group_id="B4">
          <title>Part 1, SAD, Cohort 3: TAK-935 1200 mg</title>
          <description>TAK-935 1200 mg, tablet, orally, once on Day 1 in fasted state.</description>
        </group>
        <group group_id="B5">
          <title>Part 2, MD, Cohort 4: Placebo</title>
          <description>TAK-935 placebo-matching tablets, orally, twice daily on Days 1 to 21 in fasted state.</description>
        </group>
        <group group_id="B6">
          <title>Part 2, MD, Cohort 4: TAK-935</title>
          <description>TAK-935 100 mg, tablets, orally, twice daily on Days 1 to 7, then up-titrated to TAK-935 200 mg, tablets, orally, twice daily, on Days 8 to 14, further up-titrated to TAK-935 300 mg, tablets, orally, twice daily on Days 15 to 21 as multiple doses with titration in the fasted state.</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="6"/>
            <count group_id="B2" value="6"/>
            <count group_id="B3" value="6"/>
            <count group_id="B4" value="6"/>
            <count group_id="B5" value="3"/>
            <count group_id="B6" value="6"/>
            <count group_id="B7" value="33"/>
          </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="39.8" spread="12.43"/>
                    <measurement group_id="B2" value="39.0" spread="12.71"/>
                    <measurement group_id="B3" value="31.5" spread="14.11"/>
                    <measurement group_id="B4" value="41.5" spread="11.20"/>
                    <measurement group_id="B5" value="37.7" spread="8.39"/>
                    <measurement group_id="B6" value="33.5" spread="7.48"/>
                    <measurement group_id="B7" value="37.1" spread="11.28"/>
                  </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="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>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="6"/>
                    <measurement group_id="B5" value="3"/>
                    <measurement group_id="B6" value="6"/>
                    <measurement group_id="B7" value="33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Asian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="6"/>
                    <measurement group_id="B5" value="3"/>
                    <measurement group_id="B6" value="6"/>
                    <measurement group_id="B7" value="33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Japan</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="6"/>
                    <measurement group_id="B5" value="3"/>
                    <measurement group_id="B6" value="6"/>
                    <measurement group_id="B7" value="33"/>
                  </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="170.5" spread="6.95"/>
                    <measurement group_id="B2" value="169.8" spread="4.02"/>
                    <measurement group_id="B3" value="167.0" spread="8.39"/>
                    <measurement group_id="B4" value="173.3" spread="5.61"/>
                    <measurement group_id="B5" value="173.7" spread="1.53"/>
                    <measurement group_id="B6" value="168.2" spread="2.64"/>
                    <measurement group_id="B7" value="170.1" spread="5.74"/>
                  </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="63.78" spread="4.392"/>
                    <measurement group_id="B2" value="59.88" spread="4.212"/>
                    <measurement group_id="B3" value="58.75" spread="5.410"/>
                    <measurement group_id="B4" value="65.47" spread="7.750"/>
                    <measurement group_id="B5" value="65.70" spread="1.778"/>
                    <measurement group_id="B6" value="61.38" spread="2.865"/>
                    <measurement group_id="B7" value="62.2" spread="5.311"/>
                  </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="21.98" spread="1.755"/>
                    <measurement group_id="B2" value="20.77" spread="1.206"/>
                    <measurement group_id="B3" value="21.05" spread="0.822"/>
                    <measurement group_id="B4" value="21.75" spread="1.473"/>
                    <measurement group_id="B5" value="21.77" spread="0.306"/>
                    <measurement group_id="B6" value="21.75" spread="1.571"/>
                    <measurement group_id="B7" value="21.49" spread="1.326"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Smoking Classification</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Never Smoked</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="4"/>
                    <measurement group_id="B5" value="3"/>
                    <measurement group_id="B6" value="4"/>
                    <measurement group_id="B7" value="25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Former Smoker</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="2"/>
                    <measurement group_id="B7" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Alcohol Classification</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Had Daily Consumption</title>
              <category_list>
                <category>
                  <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="2"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Had a Few Times Per Week</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="2"/>
                    <measurement group_id="B7" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Had a Few Times Per Month</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="1"/>
                    <measurement group_id="B7" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Had no Consumption</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="3"/>
                    <measurement group_id="B6" value="3"/>
                    <measurement group_id="B7" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Caffeine Classification</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Had Caffeine</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="3"/>
                    <measurement group_id="B5" value="1"/>
                    <measurement group_id="B6" value="1"/>
                    <measurement group_id="B7" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Had no Caffeine</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="3"/>
                    <measurement group_id="B5" value="2"/>
                    <measurement group_id="B6" value="5"/>
                    <measurement group_id="B7" value="23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Parts 1 and 2: Percentage of Participants With at Least One Treatment-emergent Adverse Event (TEAE)</title>
        <time_frame>Part 1: Baseline up to Day 8; Part 2: Baseline up to Day 35</time_frame>
        <population>The safety analysis set included all participants who received at least 1 dose of study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1, SAD, Cohorts 1 to 3: Placebo</title>
            <description>TAK-935 placebo-matching tablet, orally, once on Day 1 in fasted state.</description>
          </group>
          <group group_id="O2">
            <title>Part 1, SAD, Cohort 1: TAK-935 200 mg</title>
            <description>TAK-935 200 mg, tablet, orally, once on Day 1 in fasted state.</description>
          </group>
          <group group_id="O3">
            <title>Part 1, SAD, Cohort 2: TAK-935 600 mg</title>
            <description>TAK-935 600 mg, tablet, orally, once on Day 1 in fasted state.</description>
          </group>
          <group group_id="O4">
            <title>Part 1, SAD, Cohort 3: TAK-935 1200 mg</title>
            <description>TAK-935 1200 mg, tablet, orally, once on Day 1 in fasted state.</description>
          </group>
          <group group_id="O5">
            <title>Part 2, MD, Cohort 4: Placebo</title>
            <description>TAK-935 placebo-matching tablets, orally, twice daily on Days 1 to 21 in fasted state.</description>
          </group>
          <group group_id="O6">
            <title>Part 2, MD, Cohort 4: TAK-935 100 mg</title>
            <description>TAK-935 100 mg, tablets, orally, twice daily on Days 1 to 7 in fasted state.</description>
          </group>
          <group group_id="O7">
            <title>Part 2, MD, Cohort 4: TAK-935 200 mg</title>
            <description>TAK-935 200 mg, tablets, orally, twice daily on Days 8 to 14 in fasted state following TAK-935 100 mg, tablet, orally, twice daily.</description>
          </group>
          <group group_id="O8">
            <title>Part 2, MD, Cohort 4: TAK-935 300 mg</title>
            <description>TAK-935 300 mg, tablets, orally, twice daily on Days 15 to 21 in fasted state following TAK-935 200 mg, tablet, orally, twice daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Parts 1 and 2: Percentage of Participants With at Least One Treatment-emergent Adverse Event (TEAE)</title>
          <population>The safety analysis set included all participants who received at least 1 dose of study drug.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="6"/>
                <count group_id="O5" value="3"/>
                <count group_id="O6" value="6"/>
                <count group_id="O7" value="6"/>
                <count group_id="O8" 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="33.33"/>
                    <measurement group_id="O7" value="16.7"/>
                    <measurement group_id="O8" value="33.33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-935</title>
        <time_frame>Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose</time_frame>
        <population>The pharmacokinetic (PK) analysis set included all participants who received at least 1 dose of study drug and had at least 1 estimable PK parameter.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1, SAD, Cohort 1: TAK-935 200 mg</title>
            <description>TAK-935 200 mg, tablet, orally, once on Day 1 in fasted state.</description>
          </group>
          <group group_id="O2">
            <title>Part 1, SAD, Cohort 2: TAK-935 600 mg</title>
            <description>TAK-935 600 mg, tablet, orally, once on Day 1 in fasted state.</description>
          </group>
          <group group_id="O3">
            <title>Part 1, SAD, Cohort 3: TAK-935 1200 mg</title>
            <description>TAK-935 1200 mg, tablet, orally, once on Day 1 in fasted state.</description>
          </group>
        </group_list>
        <measure>
          <title>Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-935</title>
          <population>The pharmacokinetic (PK) analysis set included all participants who received at least 1 dose of study drug and had at least 1 estimable PK parameter.</population>
          <units>nanogram per milliliter (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_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="413.2" spread="202.4"/>
                    <measurement group_id="O2" value="3001" spread="47.3"/>
                    <measurement group_id="O3" value="9278" spread="48.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Part 2, Cmax: Maximum Observed Plasma Concentration for TAK-935</title>
        <time_frame>Days 7, 14, and 21 pre-dose and at multiple time points (up to 12 hours) post-dose</time_frame>
        <population>The PK analysis set included all participants who received at least 1 dose of study drug and had at least 1 estimable PK parameter. As planned data for this outcome measure was collected, analyzed and reported for dose level TAK-935-100 mg on Day 7, dose level TAK-935-200 mg on Day 14, and TAK-935-300 mg on Day 21.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 2, MD, Cohort 4: TAK-935 100 mg</title>
            <description>TAK-935 100 mg, tablets, orally, twice daily on Days 1 to 7 in fasted state.</description>
          </group>
          <group group_id="O2">
            <title>Part 2, MD, Cohort 4: TAK-935 200 mg</title>
            <description>TAK-935 200 mg, tablets, orally, twice daily on Days 8 to 14 in fasted state following TAK-935 100 mg, tablet, orally, twice daily.</description>
          </group>
          <group group_id="O3">
            <title>Part 2, MD, Cohort 4: TAK-935 300 mg</title>
            <description>TAK-935 300 mg, tablets, orally, twice daily on Days 15 to 21 in fasted state following TAK-935 200 mg, tablet, orally, twice daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Part 2, Cmax: Maximum Observed Plasma Concentration for TAK-935</title>
          <population>The PK analysis set included all participants who received at least 1 dose of study drug and had at least 1 estimable PK parameter. As planned data for this outcome measure was collected, analyzed and reported for dose level TAK-935-100 mg on Day 7, dose level TAK-935-200 mg on Day 14, and TAK-935-300 mg on Day 21.</population>
          <units>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_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="146.5" spread="113.1"/>
                    <measurement group_id="O2" value="835.5" spread="73.8"/>
                    <measurement group_id="O3" value="1945" spread="37.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Part 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for TAK-935</title>
        <time_frame>Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose</time_frame>
        <population>The PK analysis set included all participants who received at least 1 dose of study drug and had at least 1 estimable PK parameter.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1, SAD, Cohort 1: TAK-935 200 mg</title>
            <description>TAK-935 200 mg, tablet, orally, once on Day 1 in fasted state.</description>
          </group>
          <group group_id="O2">
            <title>Part 1, SAD, Cohort 2: TAK-935 600 mg</title>
            <description>TAK-935 600 mg, tablet, orally, once on Day 1 in fasted state.</description>
          </group>
          <group group_id="O3">
            <title>Part 1, SAD, Cohort 3: TAK-935 1200 mg</title>
            <description>TAK-935 1200 mg, tablet, orally, once on Day 1 in fasted state.</description>
          </group>
        </group_list>
        <measure>
          <title>Part 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for TAK-935</title>
          <population>The PK analysis set included all participants who received at least 1 dose of study drug and had at least 1 estimable PK parameter.</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_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="512.7" spread="100.8"/>
                    <measurement group_id="O2" value="3538" spread="45.8"/>
                    <measurement group_id="O3" value="10590" spread="42.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Part 1, AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Time of Infinity for TAK-935</title>
        <time_frame>Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose</time_frame>
        <population>The PK analysis set included all participants who received at least 1 dose of study drug and had at least 1 estimable PK parameter.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1, SAD, Cohort 1: TAK-935 200 mg</title>
            <description>TAK-935 200 mg, tablet, orally, once on Day 1 in fasted state.</description>
          </group>
          <group group_id="O2">
            <title>Part 1, SAD, Cohort 2: TAK-935 600 mg</title>
            <description>TAK-935 600 mg, tablet, orally, once on Day 1 in fasted state.</description>
          </group>
          <group group_id="O3">
            <title>Part 1, SAD, Cohort 3: TAK-935 1200 mg</title>
            <description>TAK-935 1200 mg, tablet, orally, once on Day 1 in fasted state.</description>
          </group>
        </group_list>
        <measure>
          <title>Part 1, AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Time of Infinity for TAK-935</title>
          <population>The PK analysis set included all participants who received at least 1 dose of study drug and had at least 1 estimable PK parameter.</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_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="539.2" spread="97.2"/>
                    <measurement group_id="O2" value="3603" spread="45.1"/>
                    <measurement group_id="O3" value="10660" spread="42.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Part 1, AUC(0-24): Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours Post-dose for TAK-935</title>
        <time_frame>Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose</time_frame>
        <population>The PK analysis set included all participants who received at least 1 dose of study drug and had at least 1 estimable PK parameter.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1, SAD, Cohort 1: TAK-935 200 mg</title>
            <description>TAK-935 200 mg, tablet, orally, once on Day 1 in fasted state.</description>
          </group>
          <group group_id="O2">
            <title>Part 1, SAD, Cohort 2: TAK-935 600 mg</title>
            <description>TAK-935 600 mg, tablet, orally, once on Day 1 in fasted state.</description>
          </group>
          <group group_id="O3">
            <title>Part 1, SAD, Cohort 3: TAK-935 1200 mg</title>
            <description>TAK-935 1200 mg, tablet, orally, once on Day 1 in fasted state.</description>
          </group>
        </group_list>
        <measure>
          <title>Part 1, AUC(0-24): Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours Post-dose for TAK-935</title>
          <population>The PK analysis set included all participants who received at least 1 dose of study drug and had at least 1 estimable PK parameter.</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_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="517.8" spread="99.4"/>
                    <measurement group_id="O2" value="3538" spread="45.8"/>
                    <measurement group_id="O3" value="10540" spread="41.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Part 2, AUCtau,ss: Area Under the Plasma Concentration-time Curve During the Dosing Interval at Steady State for TAK-935</title>
        <time_frame>Days 7, 14, and 21 pre-dose and at multiple time points (up to 12 hours) post-dose</time_frame>
        <population>The PK analysis set included all participants who received at least 1 dose of study drug and had at least 1 estimable PK parameter. As planned data for this outcome measure was collected, analyzed and reported for dose level TAK-935-100 mg on Day 7, dose level TAK-935-200 mg on Day 14, and TAK-935-300 mg on Day 21.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 2, MD, Cohort 4: TAK-935 100 mg</title>
            <description>TAK-935 100 mg, tablets, orally, twice daily on Days 1 to 7 in fasted state.</description>
          </group>
          <group group_id="O2">
            <title>Part 2, MD, Cohort 4: TAK-935 200 mg</title>
            <description>TAK-935 200 mg, tablets, orally, twice daily on Days 8 to 14 in fasted state following TAK-935 100 mg, tablet, orally, twice daily.</description>
          </group>
          <group group_id="O3">
            <title>Part 2, MD, Cohort 4: TAK-935 300 mg</title>
            <description>TAK-935 300 mg, tablets, orally, twice daily on Days 15 to 21 in fasted state following TAK-935 200 mg, tablet, orally, twice daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Part 2, AUCtau,ss: Area Under the Plasma Concentration-time Curve During the Dosing Interval at Steady State for TAK-935</title>
          <population>The PK analysis set included all participants who received at least 1 dose of study drug and had at least 1 estimable PK parameter. As planned data for this outcome measure was collected, analyzed and reported for dose level TAK-935-100 mg on Day 7, dose level TAK-935-200 mg on Day 14, and TAK-935-300 mg on Day 21.</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_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="202.3" spread="54.6"/>
                    <measurement group_id="O2" value="788.6" spread="48.9"/>
                    <measurement group_id="O3" value="1960" spread="27.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>TEAEs were adverse events that started after the first dose of study drug (Baseline) up to Day 8 in Part 1, and up to Day 35 in Part 2</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>Part 1, SAD, Cohort 1-3: Placebo</title>
          <description>TAK-935 placebo-matching tablet, orally, once on Day 1 in fasted state.</description>
        </group>
        <group group_id="E2">
          <title>Part 1, SAD, Cohort 1: TAK-935 200 mg</title>
          <description>TAK-935 200 mg, tablet, orally, once on Day 1 in fasted state.</description>
        </group>
        <group group_id="E3">
          <title>Part 1, SAD, Cohort 2: TAK-935 600 mg</title>
          <description>TAK-935 600 mg, tablet, orally, once on Day 1 in fasted state.</description>
        </group>
        <group group_id="E4">
          <title>Part 1, SAD, Cohort 3: TAK-935 1200 mg</title>
          <description>TAK-935 1200 mg, tablet, orally, once on Day 1 in fasted state.</description>
        </group>
        <group group_id="E5">
          <title>Part 2, MD, Cohort 4: Placebo</title>
          <description>TAK-935 placebo-matching tablets, orally, twice daily on Days 1to 21 in fasted state.</description>
        </group>
        <group group_id="E6">
          <title>Part 2, MD, Cohort 4: TAK-935 100 mg</title>
          <description>TAK-935 100 mg, tablets, orally, twice daily on Days 1 to 7 in fasted state.</description>
        </group>
        <group group_id="E7">
          <title>Part 2, MD, Cohort 4: TAK-935 200 mg</title>
          <description>TAK-935 200 mg, tablets, orally, twice daily on Days 8 to 14 in fasted state following TAK-935 100 mg, tablet, orally, twice daily.</description>
        </group>
        <group group_id="E8">
          <title>Part 2, MD, Cohort 4: TAK-935 300 mg</title>
          <description>TAK-935 300 mg, tablets, orally, twice daily on Days 15 to 21 in fasted state following TAK-935 200 mg, tablet, orally, twice daily.</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="6"/>
                <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="3"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E8" 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="6"/>
                <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="3"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA23.0</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="0" subjects_at_risk="6"/>
                <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="3"/>
                <counts group_id="E6" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="2" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <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="3"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Hiccups</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <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="3"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Alopecia areata</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <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="3"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <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="3"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <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="3"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E8" 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>Study 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/NCT04461483
org study id: TAK-935-1004
secondary id: U1111-1252-8555
secondary id: JapicCTI-205349
nct id: NCT04461483
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and
      pharmacodynamics of TAK-935 with single ascending doses (Part 1) and multiple doses with
      titration (Part 2).
The drug being tested in this study is called TAK-935 tablet. TAK-935 tablet is being tested
      in Japanese healthy adult men. This study will evaluate the safety, tolerability,
      pharmacokinetics, and pharmacodynamics of TAK-935 with single ascending doses (Part 1) and
      multiple doses with titration (Part 2).

      The study will enroll up to 33 participants in total (Part 1 + 2). In Part 1, participants
      will be randomly assigned (by chance, like flipping a coin) to one of these treatment
      cohorts/groups;

        -  Cohort 1: Single dose of TAK-935 at 200 mg or placebo (fasted)

        -  Cohort 2: Single dose of TAK-935 at 600 mg or placebo (fasted)

        -  Cohort 3: Single dose of TAK-935 at 1200 mg or placebo (fasted)

      In Part 2, participants will be randomly assigned to one of these treatment groups;

      - Cohort 4: Multiple doses with titration of TAK-935 or placebo at 100 mg twice daily (BID)
      from Day 1 to Day 7, 200 mg BID from Day 8 to Day 14 and 300 mg BID from Day 15 to Day 21
      (fasted).

      This single-center trial will be conducted in Japan. The overall time to participate in this
      study is approximately 36 days for Part 1 and 63 days for Part 2. Participants will be
      hospitalized for 5 days in Part 1 and 26 days in Part 2.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Parts 1 and 2: Percentage of Participants With at Least One Treatment-emergent Adverse Event (TEAE)
time frame: Part 1: Baseline up to Day 8; Part 2: Baseline up to Day 35
measure: Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-935
time frame: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose
measure: Part 2, Cmax: Maximum Observed Plasma Concentration for TAK-935
time frame: Days 7, 14, and 21 pre-dose and at multiple time points (up to 12 hours) post-dose
measure: Part 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for TAK-935
time frame: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose
measure: Part 1, AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Time of Infinity for TAK-935
time frame: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose
measure: Part 1, AUC(0-24): Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours Post-dose for TAK-935
time frame: Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose
measure: Part 2, AUCtau,ss: Area Under the Plasma Concentration-time Curve During the Dosing Interval at Steady State for TAK-935
time frame: Days 7, 14, and 21 pre-dose and at multiple time points (up to 12 hours) post-dose
arm group label: Part 1, Cohort 1; TAK-935 200 mg
arm group type: Experimental
description: Part 1, Cohort 1; TAK-935 200 mg, tablets, orally once on Days 1 in fasted state.
arm group label: Part 1, Cohort 2; TAK-935 600 mg
arm group type: Experimental
description: Part 1, Cohort 2; TAK-935 600 mg, tablets, orally once on Days 1 in fasted state.
arm group label: Part 1, Cohort 3; TAK-935 1200 mg
arm group type: Experimental
description: Part 1, Cohort 3; TAK-935 1200 mg, tablets, orally once on Days 1 in fasted state.
arm group label: Part 1, Cohort 1-3; Placebo
arm group type: Placebo Comparator
description: Part 1, Cohort 1-3; TAK-935 placebo-matching tablets, orally once on Days 1 in fasted state.
arm group label: Part 2, Cohort 4: TAK-935 100 mg
arm group type: Experimental
description: Part 2, Cohort 4: TAK-935 100 mg, tablets, orally twice on Days 1-7 in fasted state with multiple doses with titration.
arm group label: Part 2, Cohort 4: TAK-935 200 mg
arm group type: Experimental
description: Part 2, Cohort 4: TAK-935 200 mg, tablets, orally twice on Days 8-14 in fasted state with multiple doses with titration.
arm group label: Part 2, Cohort 4: TAK-935 300 mg
arm group type: Experimental
description: Part 2, Cohort 4: TAK-935 300 mg, tablets, orally twice on Days 15-21 in fasted state with multiple doses with titration.
arm group label: Part 2, Cohort 4: Placebo
arm group type: Placebo Comparator
description: Part 2, Cohort 4: TAK-935 placebo-matching tablets, orally twice on Days 1-21 in fasted state.
intervention type: Drug
intervention name: TAK-935
description: TAK-935 Tablets
arm group label: Part 1, Cohort 1; TAK-935 200 mg
arm group label: Part 1, Cohort 2; TAK-935 600 mg
arm group label: Part 1, Cohort 3; TAK-935 1200 mg
arm group label: Part 2, Cohort 4: TAK-935 100 mg
arm group label: Part 2, Cohort 4: TAK-935 200 mg
arm group label: Part 2, Cohort 4: TAK-935 300 mg
intervention type: Drug
intervention name: Placebo
description: TAK-935 placebo-matching tablets
arm group label: Part 1, Cohort 1-3; Placebo
arm group label: Part 2, Cohort 4: Placebo
criteria: 
gender: All
minimum age: 20 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Study Director
role: Study Director
affiliation: Takeda
facility: 
country: Japan
responsible party type: Sponsor
sharing ipd: Yes
ipd description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd access criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
ipd url: https://vivli.org/ourmember/takeda/
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 