<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/NCT03808493</url>
  </required_header>
  <id_info>
    <org_study_id>TAK-438ODT-1001</org_study_id>
    <secondary_id>U1111-1225-5005</secondary_id>
    <secondary_id>JapicCTI-194587</secondary_id>
    <nct_id>NCT03808493</nct_id>
  </id_info>
  <brief_title>A Bioequivalence (BE) Study of TAK-438 Orally Disintegrating (OD) Tablet</brief_title>
  <official_title>A Randomized, Open-Label, Single-Dose, 2×2 Crossover Phase 1 Study to Evaluate the Bioequivalence of TAK-438 OD (Orally Disintegrating) 20 mg Tablet When Administered Without Water (Study 1) or With Water (Study 2) and TAK-438 20 mg Tablet When Administered With Water in Japanese Healthy Volunteer Male 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 BE of single oral dose of TAK-438 OD 20&#xD;
      milligram (mg) tablet without water and TAK-438 20 mg tablet with water (Study 1), and&#xD;
      TAK-438 OD 20 mg tablet with water and TAK-438 20 mg tablet with water (Study 2) in Japanese&#xD;
      healthy adult male participants.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The drug being tested in this study is called TAK-438 OD tablet. TAK-438 OD tablet is being&#xD;
      tested in Japanese healthy adult men. This study will evaluate bioequivalence of single oral&#xD;
      dose of TAK-438 OD 20 mg tablet without water and TAK-438 20 mg tablet with water (Study 1),&#xD;
      and TAK-438 OD 20 mg tablet with water and TAK-438 20 mg tablet with water (Study 2).&#xD;
&#xD;
      The study will enroll up to 144 participants in total (Study 1 + 2). In Study 1 and 2,&#xD;
      participants will be randomly assigned (by chance, like flipping a coin) to one of the two&#xD;
      treatment groups;&#xD;
&#xD;
      Study 1:&#xD;
&#xD;
        -  TAK-438 OD 20 mg tablet without water (Period 1) + TAK-438 20 mg tablet with water&#xD;
           (Period 2)&#xD;
&#xD;
        -  TAK-438 20 mg tablet with water (Period 1) + TAK-438 OD 20 mg tablet without water&#xD;
           (Period 2)&#xD;
&#xD;
      Study 2:&#xD;
&#xD;
        -  TAK-438 OD 20 mg tablet with water (Period 1) + TAK-438 20 mg tablet with water (Period&#xD;
           2)&#xD;
&#xD;
        -  TAK-438 20 mg tablet with water (Period 1) + TAK-438 OD 20 mg tablet with water (Period&#xD;
           2)&#xD;
&#xD;
      This single-center trial will be conducted in Japan. The overall time to participate in this&#xD;
      study is approximately 11 days. Participants will make two visits to the clinic and be&#xD;
      hospitalized for four days each in Periods 1 and 2.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 30, 2019</start_date>
  <completion_date type="Actual">March 12, 2019</completion_date>
  <primary_completion_date type="Actual">March 12, 2019</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>Crossover Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Plasma Concentration for TAK-438 Free Base (TAK-438F)</measure>
    <time_frame>Day 1 pre-dose and at multiple time points (up to 48 hours; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours) post-dose</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Cmax: Maximum Observed Plasma Concentration for TAK-438F</measure>
    <time_frame>Day 1 pre-dose and at multiple time points (up to 48 hours; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours) post-dose</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-438F</measure>
    <time_frame>Day 1 pre-dose and at multiple time points (up to 48 hours; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours) post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tmax: Time of First Occurrence of Maximum Plasma Concentration (Cmax) for TAK-438F</measure>
    <time_frame>Day 1 pre-dose and at multiple time points (up to 48 hours; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours) post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MRT∞,ev: Mean Residence Time After Extravascular Administration From Time 0 to Infinity for TAK-438F</measure>
    <time_frame>Day 1 pre-dose and at multiple time points (up to 48 hours; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours) post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>λz: Terminal Disposition Phase Rate Constant for TAK-438F</measure>
    <time_frame>Day 1 pre-dose and at multiple time points (up to 48 hours; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours) post-dose</time_frame>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">48</enrollment>
  <condition>Japanese Healthy Adult Male</condition>
  <arm_group>
    <arm_group_label>Study 1, TAK-438 OD + TAK-438</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>One TAK-438 OD 20 mg tablet, orally without water under fasted condition, on Period 1 Day 1 in Study 1 (Day 1), followed by a wash-out period (Days 2 to 8), followed by one TAK-438 20 mg tablet, orally with water under fasted condition, on Period 2 Day 1 in Study 1 (Day 9).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Study 1, TAK-438 + TAK-438 OD</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>One TAK-438 20 mg tablet, orally with water under fasted condition, on Period 1 Day 1 in Study 1 (Day 1), followed by a wash-out period (Days 2 to 8), followed by one TAK-438 OD 20 mg tablet, orally without water under fasted condition, on Period 2 Day 1 in Study 1 (Day 9).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Study 2, TAK-438 OD + TAK-438</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>One TAK-438 OD 20 mg tablet, orally with water under fasted condition, on Period 1 Day 1 in Study 2 (Day 1), followed by a wash-out period (Days 2 to 8), followed by one TAK-438 20 mg tablet, orally with water under fasted condition, on Period 2 Day 1 in Study 2 (Day 9).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Study 2, TAK-438 + TAK-438 OD</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>One TAK-438 20 mg tablet, orally with water under fasted condition, on Period 1 Day 1 in Study 2 (Day 1), followed by a wash-out period (Days 2 to 8), followed by one TAK-438 OD 20 mg tablet, orally with water under fasted condition, on Period 2 Day 1 in Study 2 (Day 9).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TAK-438 OD</intervention_name>
    <description>TAK-438 OD tablet</description>
    <arm_group_label>Study 1, TAK-438 + TAK-438 OD</arm_group_label>
    <arm_group_label>Study 1, TAK-438 OD + TAK-438</arm_group_label>
    <arm_group_label>Study 2, TAK-438 + TAK-438 OD</arm_group_label>
    <arm_group_label>Study 2, TAK-438 OD + TAK-438</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TAK-438</intervention_name>
    <description>TAK-438 tablet</description>
    <arm_group_label>Study 1, TAK-438 + TAK-438 OD</arm_group_label>
    <arm_group_label>Study 1, TAK-438 OD + TAK-438</arm_group_label>
    <arm_group_label>Study 2, TAK-438 + TAK-438 OD</arm_group_label>
    <arm_group_label>Study 2, TAK-438 OD + TAK-438</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. In the opinion of the investigator or sub-investigator, the participant is capable of&#xD;
             understanding and complying with protocol requirements.&#xD;
&#xD;
          2. The participant signs and dates a written, informed consent form prior to the&#xD;
             initiation of any study procedures.&#xD;
&#xD;
          3. The participant is a healthy Japanese adult male, aged 20 to 60 years, inclusive, at&#xD;
             the time of informed consent.&#xD;
&#xD;
          4. The participant weighs at least 50 kilogram (kg) and has a body mass index (BMI) from&#xD;
             18.5 to 25.0 kilogram per square meter (kg/m^2), inclusive at Screening.&#xD;
&#xD;
          5. The participant must be a current nonsmoker who has not used tobacco- or&#xD;
             nicotine-containing products (example, nicotine patch) for at least 6 months prior to&#xD;
             the start of study drug administration in Period 1.&#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 (ECG), and vital sign measurements performed at&#xD;
             the Screening Visit and prior to the start of study drug administration in Period 1.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. The participant has received any investigational compound within 16 weeks (112 days)&#xD;
             prior to the start of study drug administration in Period 1.&#xD;
&#xD;
          2. The participant has received TAK-438 in a previous clinical study or as a therapeutic&#xD;
             agent.&#xD;
&#xD;
          3. The participant is an immediate family member of or a study site employee, or is in a&#xD;
             dependent relationship with a study site employee who is involved in the conduct of&#xD;
             this study (example, spouse, parent, child, sibling) or may consent under duress.&#xD;
&#xD;
          4. The participant has uncontrolled, clinically significant neurologic, cardiovascular,&#xD;
             pulmonary, hepatic, renal, metabolic, gastrointestinal, urologic, or endocrine disease&#xD;
             or other abnormality (other than the disease being studied), which may impact the&#xD;
             ability of the participant to participate in the study or potentially confound its&#xD;
             results.&#xD;
&#xD;
          5. The participant has hypersensitivity to any component of TAK-438 OD tablet or TAK-438&#xD;
             tablet.&#xD;
&#xD;
          6. The participant has a positive urine drug result for drugs of abuse at Screening.&#xD;
&#xD;
          7. The participant has a history of drug or alcohol abuse within 2 years prior to the&#xD;
             Screening visit or is unwilling to agree to abstain from alcohol and drugs throughout&#xD;
             the study.&#xD;
&#xD;
          8. The participant has taken any excluded medication, supplements, or food products&#xD;
             during the specified time periods.&#xD;
&#xD;
          9. The participant has current or recent (within 6 months) gastrointestinal disease that&#xD;
             would be expected to influence the absorption of drugs (ie, a history of&#xD;
             malabsorption, esophageal reflux, peptic ulcer disease, erosive esophagitis), frequent&#xD;
             (more than once per week) occurrence of heartburn, or any surgical intervention.&#xD;
&#xD;
         10. The participant has a history of cancer, except basal cell carcinoma which has been in&#xD;
             remission for at least 5 years prior to Day 1.&#xD;
&#xD;
         11. The participant has a positive test result for hepatitis B virus surface antigen&#xD;
             (HBsAg), hepatitis C virus (HCV) antibody, human immunodeficiency virus (HIV)&#xD;
             antibody/antigen, or serological reactions for syphilis at Screening.&#xD;
&#xD;
         12. The participant has poor peripheral venous access.&#xD;
&#xD;
         13. The participant has undergone whole blood collection of at least 200 milliliter (mL)&#xD;
             within 4 weeks (28 days) or at least 400 mL within 12 weeks (84 days) prior to the&#xD;
             start of study drug administration in Period 1.&#xD;
&#xD;
         14. The participant has undergone whole blood collection of at least 800 mL in total&#xD;
             within 52 weeks (364 days) prior to the start of study drug administration in Period&#xD;
             1.&#xD;
&#xD;
         15. The participant has undergone blood component collection within 2 weeks (14 days)&#xD;
             prior to the start of study drug administration in Period 1.&#xD;
&#xD;
         16. The participant has a Screening or Check-in (Day -1) ECG that was abnormal (clinically&#xD;
             significant).&#xD;
&#xD;
         17. The participant has abnormal Screening laboratory values that suggest a clinically&#xD;
             significant underlying disease or participant with the following laboratory&#xD;
             abnormalities: alanine aminotransferase (ALT) or aspartate aminotransferase (AST)&#xD;
             above the upper limits of normal (ULN).&#xD;
&#xD;
         18. The participant who, in the opinion of the investigator or sub-investigator, is&#xD;
             unlikely to comply with the protocol or is unsuitable for any other reason.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <gender_based>Yes</gender_based>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>60 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>Sekino Clinical Pharmacology Clininc</name>
      <address>
        <city>Toshima-ku</city>
        <state>Tokyo</state>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Japan</country>
  </location_countries>
  <verification_date>March 2020</verification_date>
  <study_first_submitted>January 16, 2019</study_first_submitted>
  <study_first_submitted_qc>January 16, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 17, 2019</study_first_posted>
  <results_first_submitted>March 9, 2020</results_first_submitted>
  <results_first_submitted_qc>March 9, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">March 24, 2020</results_first_posted>
  <last_update_submitted>March 27, 2020</last_update_submitted>
  <last_update_submitted_qc>March 27, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">April 7, 2020</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 for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com 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>December 12, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/93/NCT03808493/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 27, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/93/NCT03808493/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 30 January 2019 to 12 March 2019.</recruitment_details>
      <pre_assignment_details>Healthy Japanese male participants were enrolled in 1 of the 2 treatment sequences to receive TAK-438 OD 20 milligram (mg) or TAK-438 20 mg with or without water in Study 1, and TAK-438 OD 20 mg or TAK-438 20 mg with water in Study 2. Study was completed with Pilot study since results from interim analysis satisfied the criteria of bioequivalence.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Pilot BE Study 1, Sequence A: TAK-438 OD 20 mg + TAK-438 20 mg</title>
          <description>TAK-438 orally disintegrating (OD) 20 mg, tablet, orally without water under fasted condition, once on Day 1 of Period 1, followed by a washout period of at least 7 days, further followed by TAK-438 20 mg, tablet, orally with water under fasted condition, once on Day 1 of Period 2.</description>
        </group>
        <group group_id="P2">
          <title>Pilot BE Study 1, Sequence B: TAK-438 20 mg + TAK-438 OD 20 mg</title>
          <description>TAK-438 20 mg, tablet, orally with water under fasted condition, once on Day 1 of Period 1 followed by a washout period of at least 7 days, further followed TAK-438 OD 20 mg, tablet, orally without water under fasted condition, once on Day 1 of Period 2.</description>
        </group>
        <group group_id="P3">
          <title>Pilot BE Study 2, Sequence C: TAK-438 OD 20 mg + TAK-438 20 mg</title>
          <description>TAK-438 OD 20 mg, tablet, orally with water under fasted condition, once on Day 1 of Period 1, followed by a washout period of at least 7 days, further followed by TAK-438 20 mg tablet, orally with water under fasted condition, once on Day 1 of Period 2.</description>
        </group>
        <group group_id="P4">
          <title>Pilot BE Study 2, Sequence D: TAK-438 20 mg + TAK-438 OD 20 mg</title>
          <description>TAK-438 20 mg, tablet, orally with water under fasted condition, once on Day 1 of Period 1, followed by a washout period of at least 7 days, further followed by TAK-438 OD 20 mg tablet, orally with water under fasted condition, once on Day 1 of Period 2.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="12"/>
                <participants group_id="P3" count="12"/>
                <participants group_id="P4" count="12"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="12"/>
                <participants group_id="P3" count="12"/>
                <participants group_id="P4" count="12"/>
              </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_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The safety analysis set was defined as all participants who received at least one dose of study drug.</population>
      <group_list>
        <group group_id="B1">
          <title>Pilot BE Study 1, Sequence A: TAK-438 OD 20 mg + TAK-438 20 mg</title>
          <description>TAK-438 OD 20 mg, tablet, orally without water under fasted condition, once on Day 1 of Period 1, followed by a washout period of at least 7 days, further followed by TAK-438 20 mg, tablet, orally with water under fasted condition, once on Day 1 of Period 2.</description>
        </group>
        <group group_id="B2">
          <title>Pilot BE Study 1, Sequence B: TAK-438 20 mg + TAK-438 OD 20 mg</title>
          <description>TAK-438 20 mg, tablet, orally with water under fasted condition, once on Day 1 of Period 1 followed by a washout period of at least 7 days, further followed TAK-438 OD 20 mg, tablet, orally without water under fasted condition, once on Day 1 of Period 2.</description>
        </group>
        <group group_id="B3">
          <title>Pilot BE Study 2, Sequence C: TAK-438 OD 20 mg + TAK-438 20 mg</title>
          <description>TAK-438 OD 20 mg, tablet, orally with water under fasted condition, once on Day 1 of Period 1, followed by a washout period of at least 7 days, further followed by TAK-438 20 mg tablet, orally with water under fasted condition, once on Day 1 of Period 2.</description>
        </group>
        <group group_id="B4">
          <title>Pilot BE Study 2, Sequence D: TAK-438 20 mg + TAK-438 OD 20 mg</title>
          <description>TAK-438 20 mg, tablet, orally with water under fasted condition, once on Day 1 of Period 1, followed by a washout period of at least 7 days, further followed by TAK-438 OD 20 mg tablet, orally with water under fasted condition, once on Day 1 of Period 2.</description>
        </group>
        <group group_id="B5">
          <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="12"/>
            <count group_id="B2" value="12"/>
            <count group_id="B3" value="12"/>
            <count group_id="B4" value="12"/>
            <count group_id="B5" value="48"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="12"/>
                    <count group_id="B2" value="12"/>
                    <count group_id="B3" value="12"/>
                    <count group_id="B4" value="12"/>
                    <count group_id="B5" value="48"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="22.1" spread="3.87"/>
                    <measurement group_id="B2" value="26.0" spread="6.74"/>
                    <measurement group_id="B3" value="26.5" spread="7.19"/>
                    <measurement group_id="B4" value="26.0" spread="6.76"/>
                    <measurement group_id="B5" value="25.1" spread="6.34"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="12"/>
                    <count group_id="B2" value="12"/>
                    <count group_id="B3" value="12"/>
                    <count group_id="B4" value="12"/>
                    <count group_id="B5" value="48"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <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_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="12"/>
                    <measurement group_id="B4" value="12"/>
                    <measurement group_id="B5" value="48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race and Ethnicity Not Collected</title>
          <population>Race and Ethnicity were not collected from any participant.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="0"/>
                    <count group_id="B4" value="0"/>
                    <count group_id="B5" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B5" 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>Japan</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="12"/>
                    <count group_id="B2" value="12"/>
                    <count group_id="B3" value="12"/>
                    <count group_id="B4" value="12"/>
                    <count group_id="B5" value="48"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="12"/>
                    <measurement group_id="B4" value="12"/>
                    <measurement group_id="B5" value="48"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="12"/>
                    <count group_id="B2" value="12"/>
                    <count group_id="B3" value="12"/>
                    <count group_id="B4" value="12"/>
                    <count group_id="B5" value="48"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="171.8" spread="4.00"/>
                    <measurement group_id="B2" value="170.0" spread="6.52"/>
                    <measurement group_id="B3" value="173.9" spread="4.32"/>
                    <measurement group_id="B4" value="172.2" spread="6.94"/>
                    <measurement group_id="B5" value="172.0" spread="5.59"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="12"/>
                    <count group_id="B2" value="12"/>
                    <count group_id="B3" value="12"/>
                    <count group_id="B4" value="12"/>
                    <count group_id="B5" value="48"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="59.83" spread="4.672"/>
                    <measurement group_id="B2" value="60.95" spread="4.720"/>
                    <measurement group_id="B3" value="63.29" spread="4.860"/>
                    <measurement group_id="B4" value="65.44" spread="6.716"/>
                    <measurement group_id="B5" value="62.38" spread="5.586"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="12"/>
                    <count group_id="B2" value="12"/>
                    <count group_id="B3" value="12"/>
                    <count group_id="B4" value="12"/>
                    <count group_id="B5" value="48"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="20.28" spread="1.817"/>
                    <measurement group_id="B2" value="21.15" spread="1.829"/>
                    <measurement group_id="B3" value="20.94" spread="1.781"/>
                    <measurement group_id="B4" value="22.03" spread="1.043"/>
                    <measurement group_id="B5" value="21.10" spread="1.718"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Caffeine Consumption</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Had caffeine consumption</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="12"/>
                    <count group_id="B2" value="12"/>
                    <count group_id="B3" value="12"/>
                    <count group_id="B4" value="12"/>
                    <count group_id="B5" value="48"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="4"/>
                    <measurement group_id="B5" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Had no caffeine consumption</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="12"/>
                    <count group_id="B2" value="12"/>
                    <count group_id="B3" value="12"/>
                    <count group_id="B4" value="12"/>
                    <count group_id="B5" value="48"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="8"/>
                    <measurement group_id="B4" value="8"/>
                    <measurement group_id="B5" value="37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Alcohol Consumption</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Drank a few times per week</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="12"/>
                    <count group_id="B2" value="12"/>
                    <count group_id="B3" value="12"/>
                    <count group_id="B4" value="12"/>
                    <count group_id="B5" value="48"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Drank a few times per month</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="12"/>
                    <count group_id="B2" value="12"/>
                    <count group_id="B3" value="12"/>
                    <count group_id="B4" value="12"/>
                    <count group_id="B5" value="48"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Never drank</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="12"/>
                    <count group_id="B2" value="12"/>
                    <count group_id="B3" value="12"/>
                    <count group_id="B4" value="12"/>
                    <count group_id="B5" value="48"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="8"/>
                    <measurement group_id="B4" value="10"/>
                    <measurement group_id="B5" value="31"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="12"/>
                    <count group_id="B2" value="12"/>
                    <count group_id="B3" value="12"/>
                    <count group_id="B4" value="12"/>
                    <count group_id="B5" value="48"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="10"/>
                    <measurement group_id="B4" value="11"/>
                    <measurement group_id="B5" value="43"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Former smoker</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="12"/>
                    <count group_id="B2" value="12"/>
                    <count group_id="B3" value="12"/>
                    <count group_id="B4" value="12"/>
                    <count group_id="B5" value="48"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <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="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Plasma Concentration for TAK-438 Free Base (TAK-438F)</title>
        <time_frame>Day 1 pre-dose and at multiple time points (up to 48 hours; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours) post-dose</time_frame>
        <population>The pharmacokinetic (PK) analysis set was defined as all participants who received at least one dose of study drug, and whose PK data were evaluable.</population>
        <group_list>
          <group group_id="O1">
            <title>Pilot BE Study 1: TAK-438 OD 20 mg</title>
            <description>TAK-438 OD 20 mg, tablet, orally without water under fasted condition, once on Day 1 of either Period 1 or 2.</description>
          </group>
          <group group_id="O2">
            <title>Pilot BE Study 1: TAK-438 20 mg</title>
            <description>TAK-438 20 mg, tablet, orally with water under fasted condition, once on Day 1 of either Period 1 or 2.</description>
          </group>
          <group group_id="O3">
            <title>Pilot BE Study 2: TAK-438 OD 20 mg</title>
            <description>TAK-438 OD 20 mg, tablet, orally with water under fasted condition, once on Day 1 of either Period 1 or 2.</description>
          </group>
          <group group_id="O4">
            <title>Pilot BE Study 2: TAK-438 20 mg</title>
            <description>TAK-438 20 mg, tablet, orally with water under fasted condition, once on Day 1 of either Period 1 or 2.</description>
          </group>
        </group_list>
        <measure>
          <title>AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Plasma Concentration for TAK-438 Free Base (TAK-438F)</title>
          <population>The pharmacokinetic (PK) analysis set was defined as all participants who received at least one dose of study drug, and whose PK data were evaluable.</population>
          <units>hour*nanogram per milliliter (h*ng/mL)</units>
          <param>Geometric Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="24"/>
                <count group_id="O2" value="24"/>
                <count group_id="O3" value="24"/>
                <count group_id="O4" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="190.2" spread="67.984"/>
                    <measurement group_id="O2" value="194.3" spread="67.693"/>
                    <measurement group_id="O3" value="201.6" spread="81.799"/>
                    <measurement group_id="O4" value="201.2" spread="75.813"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>For log-transformed (natural log) AUClast, the two-sided 90% CI of the difference in the least square means (LS-Means) between the formulations (TAK-438 OD tablet-TAK-438 tablet) was provided using the ANOVA model.</non_inferiority_desc>
            <param_type>LS-Means Difference</param_type>
            <param_value>-0.0211</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.0752</ci_lower_limit>
            <ci_upper_limit>0.0329</ci_upper_limit>
          </analysis>
          <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>For log-transformed (natural log) AUClast, the two-sided 90% CI of the difference in the LS-Means between the formulations (TAK-438 OD tablet-TAK-438 tablet) was provided using the ANOVA model.</non_inferiority_desc>
            <param_type>LS-Means Difference</param_type>
            <param_value>0.0019</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.0778</ci_lower_limit>
            <ci_upper_limit>0.0815</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Cmax: Maximum Observed Plasma Concentration for TAK-438F</title>
        <time_frame>Day 1 pre-dose and at multiple time points (up to 48 hours; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours) post-dose</time_frame>
        <population>The PK analysis set was defined as all participants who received at least one dose of study drug, and whose PK data were evaluable.</population>
        <group_list>
          <group group_id="O1">
            <title>Pilot BE Study 1: TAK-438 OD 20 mg</title>
            <description>TAK-438 OD 20 mg, tablet, orally without water under fasted condition, once on Day 1 of either Period 1 or 2.</description>
          </group>
          <group group_id="O2">
            <title>Pilot BE Study 1: TAK-438 20 mg</title>
            <description>TAK-438 20 mg, tablet, orally with water under fasted condition, once on Day 1 of either Period 1 or 2.</description>
          </group>
          <group group_id="O3">
            <title>Pilot BE Study 2: TAK-438 OD 20 mg</title>
            <description>TAK-438 OD 20 mg, tablet, orally with water under fasted condition, once on Day 1 of either Period 1 or 2.</description>
          </group>
          <group group_id="O4">
            <title>Pilot BE Study 2: TAK-438 20 mg</title>
            <description>TAK-438 20 mg, tablet, orally with water under fasted condition, once on Day 1 of either Period 1 or 2.</description>
          </group>
        </group_list>
        <measure>
          <title>Cmax: Maximum Observed Plasma Concentration for TAK-438F</title>
          <population>The PK analysis set was defined as all participants who received at least one dose of study drug, and whose PK data were evaluable.</population>
          <units>nanogram per milliliter (ng/mL)</units>
          <param>Geometric Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="24"/>
                <count group_id="O2" value="24"/>
                <count group_id="O3" value="24"/>
                <count group_id="O4" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22.62" spread="7.8152"/>
                    <measurement group_id="O2" value="24.26" spread="8.0676"/>
                    <measurement group_id="O3" value="21.85" spread="7.7286"/>
                    <measurement group_id="O4" value="23.70" spread="8.5998"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>For log-transformed (natural log) Cmax, the two-sided 90% CI of the difference in the LS-Means between the formulations (TAK-438 OD tablet-TAK-438 tablet) was provided using the ANOVA model.</non_inferiority_desc>
            <param_type>LS-Means Difference</param_type>
            <param_value>-0.0698</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.1404</ci_lower_limit>
            <ci_upper_limit>0.0008</ci_upper_limit>
          </analysis>
          <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>For log-transformed (natural log) Cmax, the two-sided 90% CI of the difference in the LS-Means between the formulations (TAK-438 OD tablet-TAK-438 tablet) was provided using the ANOVA model.</non_inferiority_desc>
            <param_type>LS-Means Difference</param_type>
            <param_value>-0.0811</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.1658</ci_lower_limit>
            <ci_upper_limit>0.0036</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-438F</title>
        <time_frame>Day 1 pre-dose and at multiple time points (up to 48 hours; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours) post-dose</time_frame>
        <population>The PK analysis set was defined as all participants who received at least one dose of study drug, and whose PK data were evaluable.</population>
        <group_list>
          <group group_id="O1">
            <title>Pilot BE Study 1: TAK-438 OD 20 mg</title>
            <description>TAK-438 OD 20 mg, tablet, orally without water under fasted condition, once on Day 1 of either Period 1 or 2.</description>
          </group>
          <group group_id="O2">
            <title>Pilot BE Study 1: TAK-438 20 mg</title>
            <description>TAK-438 20 mg, tablet, orally with water under fasted condition, once on Day 1 of either Period 1 or 2.</description>
          </group>
          <group group_id="O3">
            <title>Pilot BE Study 2: TAK-438 OD 20 mg</title>
            <description>TAK-438 OD 20 mg, tablet, orally with water under fasted condition, once on Day 1 of either Period 1 or 2.</description>
          </group>
          <group group_id="O4">
            <title>Pilot BE Study 2: TAK-438 20 mg</title>
            <description>TAK-438 20 mg, tablet, orally with water under fasted condition, once on Day 1 of either Period 1 or 2.</description>
          </group>
        </group_list>
        <measure>
          <title>AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-438F</title>
          <population>The PK analysis set was defined as all participants who received at least one dose of study drug, and whose PK data were evaluable.</population>
          <units>h*ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="24"/>
                <count group_id="O2" value="24"/>
                <count group_id="O3" value="24"/>
                <count group_id="O4" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="192.5" spread="68.755"/>
                    <measurement group_id="O2" value="196.4" spread="68.436"/>
                    <measurement group_id="O3" value="204.3" spread="83.014"/>
                    <measurement group_id="O4" value="203.6" spread="77.630"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>For log-transformed (natural log) AUC∞, the two-sided 90% CI of the difference in the LS-Means between the formulations (TAK-438 OD tablet-TAK-438 tablet) was provided using the ANOVA model.</non_inferiority_desc>
            <param_type>LS-Means Difference</param_type>
            <param_value>-0.0199</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.0731</ci_lower_limit>
            <ci_upper_limit>0.0333</ci_upper_limit>
          </analysis>
          <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>For log-transformed (natural log) AUC∞, the two-sided 90% CI of the difference in the LS-Means between the formulations (TAK-438 OD tablet-TAK-438 tablet) was provided using the ANOVA model.</non_inferiority_desc>
            <param_type>LS-Means Difference</param_type>
            <param_value>0.0035</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.0760</ci_lower_limit>
            <ci_upper_limit>0.0830</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Tmax: Time of First Occurrence of Maximum Plasma Concentration (Cmax) for TAK-438F</title>
        <time_frame>Day 1 pre-dose and at multiple time points (up to 48 hours; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours) post-dose</time_frame>
        <population>The PK analysis set was defined as all participants who received at least one dose of study drug, and whose PK data were evaluable.</population>
        <group_list>
          <group group_id="O1">
            <title>Pilot BE Study 1: TAK-438 OD 20 mg</title>
            <description>TAK-438 OD 20 mg, tablet, orally without water under fasted condition, once on Day 1 of either Period 1 or 2.</description>
          </group>
          <group group_id="O2">
            <title>Pilot BE Study 1: TAK-438 20 mg</title>
            <description>TAK-438 20 mg, tablet, orally with water under fasted condition, once on Day 1 of either Period 1 or 2.</description>
          </group>
          <group group_id="O3">
            <title>Pilot BE Study 2: TAK-438 OD 20 mg</title>
            <description>TAK-438 OD 20 mg, tablet, orally with water under fasted condition, once on Day 1 of either Period 1 or 2.</description>
          </group>
          <group group_id="O4">
            <title>Pilot BE Study 2: TAK-438 20 mg</title>
            <description>TAK-438 20 mg, tablet, orally with water under fasted condition, once on Day 1 of either Period 1 or 2.</description>
          </group>
        </group_list>
        <measure>
          <title>Tmax: Time of First Occurrence of Maximum Plasma Concentration (Cmax) for TAK-438F</title>
          <population>The PK analysis set was defined as all participants who received at least one dose of study drug, and whose PK data were evaluable.</population>
          <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="24"/>
                <count group_id="O2" value="24"/>
                <count group_id="O3" value="24"/>
                <count group_id="O4" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.000" lower_limit="1.00" upper_limit="4.00"/>
                    <measurement group_id="O2" value="1.750" lower_limit="1.00" upper_limit="3.00"/>
                    <measurement group_id="O3" value="2.000" lower_limit="1.00" upper_limit="4.00"/>
                    <measurement group_id="O4" value="2.000" lower_limit="1.00" upper_limit="4.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>For log-transformed (natural log) Tmax, the two-sided 90% CI of the difference in the LS-Means between the formulations (TAK-438 OD tablet-TAK-438 tablet) was provided using the ANOVA model.</non_inferiority_desc>
            <param_type>LS-Means Difference</param_type>
            <param_value>0.1902</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.0199</ci_lower_limit>
            <ci_upper_limit>0.3605</ci_upper_limit>
          </analysis>
          <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>For log-transformed (natural log) Tmax, the two-sided 90% CI of the difference in the LS-Means between the formulations (TAK-438 OD tablet-TAK-438 tablet) was provided using the ANOVA model.</non_inferiority_desc>
            <param_type>LS-Means Difference</param_type>
            <param_value>0.2142</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.0558</ci_lower_limit>
            <ci_upper_limit>0.3725</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>MRT∞,ev: Mean Residence Time After Extravascular Administration From Time 0 to Infinity for TAK-438F</title>
        <time_frame>Day 1 pre-dose and at multiple time points (up to 48 hours; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours) post-dose</time_frame>
        <population>The PK analysis set was defined as all participants who received at least one dose of study drug, and whose PK data were evaluable.</population>
        <group_list>
          <group group_id="O1">
            <title>Pilot BE Study 1: TAK-438 OD 20 mg</title>
            <description>TAK-438 OD 20 mg, tablet, orally without water under fasted condition, once on Day 1 of either Period 1 or 2.</description>
          </group>
          <group group_id="O2">
            <title>Pilot BE Study 1: TAK-438 20 mg</title>
            <description>TAK-438 20 mg, tablet, orally with water under fasted condition, once on Day 1 of either Period 1 or 2.</description>
          </group>
          <group group_id="O3">
            <title>Pilot BE Study 2: TAK-438 OD 20 mg</title>
            <description>TAK-438 OD 20 mg, tablet, orally with water under fasted condition, once on Day 1 of either Period 1 or 2.</description>
          </group>
          <group group_id="O4">
            <title>Pilot BE Study 2: TAK-438 20 mg</title>
            <description>TAK-438 20 mg, tablet, orally with water under fasted condition, once on Day 1 of either Period 1 or 2.</description>
          </group>
        </group_list>
        <measure>
          <title>MRT∞,ev: Mean Residence Time After Extravascular Administration From Time 0 to Infinity for TAK-438F</title>
          <population>The PK analysis set was defined as all participants who received at least one dose of study drug, and whose PK data were evaluable.</population>
          <units>hour</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="24"/>
                <count group_id="O2" value="24"/>
                <count group_id="O3" value="24"/>
                <count group_id="O4" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.576" spread="1.1807"/>
                    <measurement group_id="O2" value="9.258" spread="0.91125"/>
                    <measurement group_id="O3" value="9.831" spread="1.3506"/>
                    <measurement group_id="O4" value="9.544" spread="1.4121"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>For log-transformed (natural log) MRT∞,ev, the two-sided 90% CI of the difference in the LS-Means between the formulations (TAK-438 OD tablet-TAK-438 tablet) was provided using the ANOVA model.</non_inferiority_desc>
            <param_type>LS-Means Difference</param_type>
            <param_value>0.0311</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.0022</ci_lower_limit>
            <ci_upper_limit>0.0599</ci_upper_limit>
          </analysis>
          <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>For log-transformed (natural log) MRT∞,ev, the two-sided 90% CI of the difference in the LS-Means between the formulations (TAK-438 OD tablet-TAK-438 tablet) was provided using the ANOVA model.</non_inferiority_desc>
            <param_type>LS-Means Difference</param_type>
            <param_value>0.0306</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.0003</ci_lower_limit>
            <ci_upper_limit>0.0616</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>λz: Terminal Disposition Phase Rate Constant for TAK-438F</title>
        <time_frame>Day 1 pre-dose and at multiple time points (up to 48 hours; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours) post-dose</time_frame>
        <population>The PK analysis set was defined as all participants who received at least one dose of study drug, and whose PK data were evaluable.</population>
        <group_list>
          <group group_id="O1">
            <title>Pilot BE Study 1: TAK-438 OD 20 mg</title>
            <description>TAK-438 OD 20 mg, tablet, orally without water under fasted condition, once on Day 1 of either Period 1 or 2.</description>
          </group>
          <group group_id="O2">
            <title>Pilot BE Study 1: TAK-438 20 mg</title>
            <description>TAK-438 20 mg, tablet, orally with water under fasted condition, once on Day 1 of either Period 1 or 2.</description>
          </group>
          <group group_id="O3">
            <title>Pilot BE Study 2: TAK-438 OD 20 mg</title>
            <description>TAK-438 OD 20 mg, tablet, orally with water under fasted condition, once on Day 1 of either Period 1 or 2.</description>
          </group>
          <group group_id="O4">
            <title>Pilot BE Study 2: TAK-438 20 mg</title>
            <description>TAK-438 20 mg, tablet, orally with water under fasted condition, once on Day 1 of either Period 1 or 2.</description>
          </group>
        </group_list>
        <measure>
          <title>λz: Terminal Disposition Phase Rate Constant for TAK-438F</title>
          <population>The PK analysis set was defined as all participants who received at least one dose of study drug, and whose PK data were evaluable.</population>
          <units>per hour (1/hour)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="24"/>
                <count group_id="O2" value="24"/>
                <count group_id="O3" value="24"/>
                <count group_id="O4" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.1014" spread="0.014441"/>
                    <measurement group_id="O2" value="0.09903" spread="0.011269"/>
                    <measurement group_id="O3" value="0.09807" spread="0.013021"/>
                    <measurement group_id="O4" value="0.09989" spread="0.016690"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>For log-transformed (natural log) λz, the two-sided 90% CI of the difference in the LS-Means between the formulations (TAK-438 OD tablet-TAK-438 tablet) was provided using the ANOVA model.</non_inferiority_desc>
            <param_type>LS-Means Difference</param_type>
            <param_value>0.0209</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.0112</ci_lower_limit>
            <ci_upper_limit>0.0530</ci_upper_limit>
          </analysis>
          <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>For log-transformed (natural log) λz, the two-sided 90% CI of the difference in the LS-Means between the formulations (TAK-438 OD tablet-TAK-438 tablet) was provided using the ANOVA model.</non_inferiority_desc>
            <param_type>LS-Means Difference</param_type>
            <param_value>-0.0135</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.0508</ci_lower_limit>
            <ci_upper_limit>0.0238</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Treatment-emergent adverse events (TEAEs) are adverse events (AE) that started after the first dose of study drug until Day 3 in Period 2 (up to Day 13)</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>Pilot BE Study 1: TAK-438 OD 20 mg</title>
          <description>TAK-438 OD 20 mg, tablet, orally without water under fasted condition, once on Day 1 of either Period 1 or 2.</description>
        </group>
        <group group_id="E2">
          <title>Pilot BE Study 1: TAK-438 20 mg</title>
          <description>TAK-438 20 mg, tablet, orally with water under fasted condition, once on Day 1 of either Period 1 or 2.</description>
        </group>
        <group group_id="E3">
          <title>Pilot BE Study 2: TAK-438 OD 20 mg</title>
          <description>TAK-438 OD 20 mg, tablet, orally with water under fasted condition, once on Day 1 of either Period 1 or 2.</description>
        </group>
        <group group_id="E4">
          <title>Pilot BE Study 2: TAK-438 20 mg</title>
          <description>TAK-438 20 mg, tablet, orally with water under fasted condition, once on Day 1 of either Period 1 or 2.</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="24"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <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="24"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="24"/>
              </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/NCT03808493
org study id: TAK-438ODT-1001
secondary id: U1111-1225-5005
secondary id: JapicCTI-194587
nct id: NCT03808493
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to evaluate the BE of single oral dose of TAK-438 OD 20
      milligram (mg) tablet without water and TAK-438 20 mg tablet with water (Study 1), and
      TAK-438 OD 20 mg tablet with water and TAK-438 20 mg tablet with water (Study 2) in Japanese
      healthy adult male participants.
The drug being tested in this study is called TAK-438 OD tablet. TAK-438 OD tablet is being
      tested in Japanese healthy adult men. This study will evaluate bioequivalence of single oral
      dose of TAK-438 OD 20 mg tablet without water and TAK-438 20 mg tablet with water (Study 1),
      and TAK-438 OD 20 mg tablet with water and TAK-438 20 mg tablet with water (Study 2).

      The study will enroll up to 144 participants in total (Study 1 + 2). In Study 1 and 2,
      participants will be randomly assigned (by chance, like flipping a coin) to one of the two
      treatment groups;

      Study 1:

        -  TAK-438 OD 20 mg tablet without water (Period 1) + TAK-438 20 mg tablet with water
           (Period 2)

        -  TAK-438 20 mg tablet with water (Period 1) + TAK-438 OD 20 mg tablet without water
           (Period 2)

      Study 2:

        -  TAK-438 OD 20 mg tablet with water (Period 1) + TAK-438 20 mg tablet with water (Period
           2)

        -  TAK-438 20 mg tablet with water (Period 1) + TAK-438 OD 20 mg tablet with water (Period
           2)

      This single-center trial will be conducted in Japan. The overall time to participate in this
      study is approximately 11 days. Participants will make two visits to the clinic and be
      hospitalized for four days each in Periods 1 and 2.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Other
masking: None (Open Label)
measure: AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Plasma Concentration for TAK-438 Free Base (TAK-438F)
time frame: Day 1 pre-dose and at multiple time points (up to 48 hours; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours) post-dose
measure: Cmax: Maximum Observed Plasma Concentration for TAK-438F
time frame: Day 1 pre-dose and at multiple time points (up to 48 hours; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours) post-dose
measure: AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-438F
time frame: Day 1 pre-dose and at multiple time points (up to 48 hours; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours) post-dose
measure: Tmax: Time of First Occurrence of Maximum Plasma Concentration (Cmax) for TAK-438F
time frame: Day 1 pre-dose and at multiple time points (up to 48 hours; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours) post-dose
measure: MRT∞,ev: Mean Residence Time After Extravascular Administration From Time 0 to Infinity for TAK-438F
time frame: Day 1 pre-dose and at multiple time points (up to 48 hours; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours) post-dose
measure: λz: Terminal Disposition Phase Rate Constant for TAK-438F
time frame: Day 1 pre-dose and at multiple time points (up to 48 hours; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours) post-dose
arm group label: Study 1, TAK-438 OD + TAK-438
arm group type: Experimental
description: One TAK-438 OD 20 mg tablet, orally without water under fasted condition, on Period 1 Day 1 in Study 1 (Day 1), followed by a wash-out period (Days 2 to 8), followed by one TAK-438 20 mg tablet, orally with water under fasted condition, on Period 2 Day 1 in Study 1 (Day 9).
arm group label: Study 1, TAK-438 + TAK-438 OD
arm group type: Experimental
description: One TAK-438 20 mg tablet, orally with water under fasted condition, on Period 1 Day 1 in Study 1 (Day 1), followed by a wash-out period (Days 2 to 8), followed by one TAK-438 OD 20 mg tablet, orally without water under fasted condition, on Period 2 Day 1 in Study 1 (Day 9).
arm group label: Study 2, TAK-438 OD + TAK-438
arm group type: Experimental
description: One TAK-438 OD 20 mg tablet, orally with water under fasted condition, on Period 1 Day 1 in Study 2 (Day 1), followed by a wash-out period (Days 2 to 8), followed by one TAK-438 20 mg tablet, orally with water under fasted condition, on Period 2 Day 1 in Study 2 (Day 9).
arm group label: Study 2, TAK-438 + TAK-438 OD
arm group type: Experimental
description: One TAK-438 20 mg tablet, orally with water under fasted condition, on Period 1 Day 1 in Study 2 (Day 1), followed by a wash-out period (Days 2 to 8), followed by one TAK-438 OD 20 mg tablet, orally with water under fasted condition, on Period 2 Day 1 in Study 2 (Day 9).
intervention type: Drug
intervention name: TAK-438 OD
description: TAK-438 OD tablet
arm group label: Study 1, TAK-438 + TAK-438 OD
arm group label: Study 1, TAK-438 OD + TAK-438
arm group label: Study 2, TAK-438 + TAK-438 OD
arm group label: Study 2, TAK-438 OD + TAK-438
intervention type: Drug
intervention name: TAK-438
description: TAK-438 tablet
arm group label: Study 1, TAK-438 + TAK-438 OD
arm group label: Study 1, TAK-438 OD + TAK-438
arm group label: Study 2, TAK-438 + TAK-438 OD
arm group label: Study 2, TAK-438 OD + TAK-438
criteria: 
gender: Male
gender based: Yes
minimum age: 20 Years
maximum age: 60 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 makes patient-level, de-identified data sets and associated documents available for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com 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: 