<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/NCT02246478</url>
  </required_header>
  <id_info>
    <org_study_id>Taiho10053030</org_study_id>
    <nct_id>NCT02246478</nct_id>
  </id_info>
  <brief_title>A Study of TAS-205 for Duchenne Muscular Dystrophy</brief_title>
  <official_title>A Phase I Study of Single and Multiple Doses of TAS-205 in Patients With Duchenne Muscular Dystrophy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Taiho Pharmaceutical Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Taiho Pharmaceutical Co., Ltd.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The objective of this study is to evaluate the safety and pharmacokinetic of TAS-205 in&#xD;
      patients with Duchenne Muscular Dystrophy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Duchenne Muscular Dystrophy (DMD) is the most common fatal genetic disorder diagnosed in&#xD;
      childhood, affecting approximately 1 in every 3500 lives male births. DMD patients suffer&#xD;
      from a relentless decline in muscle strength that impairs the ability of walking and&#xD;
      breathing, resulting in their lives with wheelchairs and loss of upper body function. The&#xD;
      objective of this study is to evaluate the safety and pharmacokinetic of TAS-205 after single&#xD;
      and multiple doses in DMD patients. It is also evaluated if TAS-205 affects the urinary&#xD;
      excretion of pharmacodynamic (PD) marker in DMD patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2014</start_date>
  <completion_date type="Actual">September 2015</completion_date>
  <primary_completion_date type="Actual">June 2015</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>Incidence of Adverse Events</measure>
    <time_frame>From the first administration day to the end of the observation period (ie. single-dose phase: 8 days, multiple-doses phase: 14 days)</time_frame>
    <description>Source Vocabulary Name for Table Default: CTCAE (4.03)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Peak Plasma Concentration (Cmax) of TAS-205</measure>
    <time_frame>Single-dose phase: immediately before dosing, 0, 0.5, 1, 2, 4, 8, 24, 48 hours post-dose, Multiple-dose phase: Days 1 and 7, immediately before morning dose, 0.5, 1, 2, 4, and 8 hours post-dose and Day 4, immediately before morning dose.</time_frame>
    <description>Due to inspection missing, some data were not analyzed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Plasma Concentration Versus Time Curve (AUC) of TAS-205</measure>
    <time_frame>Administration period (ie. single-dose phase: from single administration day to 48 hours after the administration, multiple-dose phase: from the first administration day to 8 hours after the last administration)</time_frame>
    <description>Due to inspection missing, some data were not analyzed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Urinary Excretion of PD Marker</measure>
    <time_frame>Single-dose: Day -1 before administration, 0-24 hr post-dose, and 24-48 hr post-dose, Multiple-doses: Day -1 before administration, 0 hr after administration on Day 1 and 4 to the following day (Day 2 and 5), and 0-24 hr after administration on Day 7.</time_frame>
    <description>Ratio of prostaglandin E2 metabolite / creatinine Due to inspection missing, some data were not analyzed.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">23</enrollment>
  <condition>Duchenne Muscular Dystrophy</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>TAS-205 low dose</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>TAS-205 middle dose</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>TAS-205 high dose</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TAS-205</intervention_name>
    <description>Single-dose phase: 3 steps (low dose, middle dose or high dose group), 5 patients/step, single oral administration after meals&#xD;
Multiple-dose phase: 3 steps (low dose, middle dose or high dose group), 5 patients/step (the same patients between single- and multiple-dose phases), repeated oral administration for 7 days, BID after meals</description>
    <arm_group_label>TAS-205 high dose</arm_group_label>
    <arm_group_label>TAS-205 low dose</arm_group_label>
    <arm_group_label>TAS-205 middle dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Single-dose phase: 3steps (low dose, middle dose or high dose group), 2 patients/step, single oral administration after meals&#xD;
Multiple-dose phase: 3 steps (low dose, middle dose or high dose group), 2 patients/step (the same patients between single- and multiple-dose phases), repeated oral administration for 7 days, BID after meals</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Able to give an informed consent. If applicable, able to give an informed assent.&#xD;
&#xD;
          -  Male and &gt;= 5 years and &lt; 16 years of age.&#xD;
&#xD;
          -  Bodyweight of &gt;= 15.0 kg and &lt; 75.0 kg.&#xD;
&#xD;
          -  Phenotypic evidence of DMD.&#xD;
&#xD;
          -  Able to take tablets.&#xD;
&#xD;
          -  If taking oral glucocorticosteroids no significant change in total daily dosage or&#xD;
             dosing regimen after enrollment.&#xD;
&#xD;
          -  Confirmed the urinary PD marker over its criteria.&#xD;
&#xD;
          -  Able to follow the study protocol.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Current diagnosis or history of any drug allergy.&#xD;
&#xD;
          -  A forced vital capacity (FVC) &lt; 50% of predicted value.&#xD;
&#xD;
          -  A left ventricular ejection fraction (EF) &lt; 50% or fractional shortening (FS) &lt; 25%&#xD;
             based on echocardiogram (ECHO).&#xD;
&#xD;
          -  Ongoing immunosuppressive therapy (other than corticosteroids).&#xD;
&#xD;
          -  With severe disease such as hepatic disease, kidney disease and others.&#xD;
&#xD;
          -  With any systemic allergic disease or any chronic inflammatory disease.&#xD;
&#xD;
          -  Treated with any other investigational agents within 90 days.&#xD;
&#xD;
          -  Positive reaction in hepatitis B surface antigen (HbsAg), hepatitis C antibody test&#xD;
             (HCV), or human immunodeficiency virus (HIV) test.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>5 Years</minimum_age>
    <maximum_age>15 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Taiho Pharmaceutical Co.,Ltd.</last_name>
    <role>Study Director</role>
    <affiliation>Taiho Pharmaceutical Co., Ltd.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>National Center of Neurology and Psychiatry</name>
      <address>
        <city>Tokyo</city>
        <zip>187-8551</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Japan</country>
  </location_countries>
  <verification_date>May 2021</verification_date>
  <study_first_submitted>September 9, 2014</study_first_submitted>
  <study_first_submitted_qc>September 18, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 22, 2014</study_first_posted>
  <results_first_submitted>March 10, 2020</results_first_submitted>
  <results_first_submitted_qc>May 11, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">June 4, 2021</results_first_posted>
  <last_update_submitted>May 11, 2021</last_update_submitted>
  <last_update_submitted_qc>May 11, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">June 4, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Muscular Dystrophies</mesh_term>
    <mesh_term>Muscular Dystrophy, Duchenne</mesh_term>
  </condition_browse>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>Two participants in 21 participants of Single-dose phase discontinued after Single-dose phase. So, 19 participants moved to Multiple-dose phase. And new two participants enrolled in Multiple-dose phase.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Placebo</title>
          <description>Placebo: ・Single-dose phase: 3steps (low dose, middle dose or high dose group), 2 patients/step, single oral administration after meals&#xD;
・Multiple-dose phase: 3 steps (low dose, middle dose or high dose group), 2 patients/step (the same patients between single- and multiple-dose phases), repeated oral administration for 7 days, BID after meals</description>
        </group>
        <group group_id="P2">
          <title>TAS-205 Low Dose</title>
          <description>TAS-205: ・Single-dose phase: 3 steps (low dose, middle dose or high dose group), 5 patients/step, single oral administration after meals&#xD;
・Multiple-dose phase: 3 steps (low dose, middle dose or high dose group), 5 patients/step (the same patients between single- and multiple-dose phases), repeated oral administration for 7 days, BID after meals</description>
        </group>
        <group group_id="P3">
          <title>TAS-205 Middle Dose</title>
          <description>TAS-205: ・Single-dose phase: 3 steps (low dose, middle dose or high dose group), 5 patients/step, single oral administration after meals&#xD;
・Multiple-dose phase: 3 steps (low dose, middle dose or high dose group), 5 patients/step (the same patients between single- and multiple-dose phases), repeated oral administration for 7 days, BID after meals</description>
        </group>
        <group group_id="P4">
          <title>TAS-205 High Dose</title>
          <description>TAS-205: ・Single-dose phase: 3 steps (low dose, middle dose or high dose group), 5 patients/step, single oral administration after meals&#xD;
・Multiple-dose phase: 3 steps (low dose, middle dose or high dose group), 5 patients/step (the same patients between single- and multiple-dose phases), repeated oral administration for 7 days, BID after meals</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Single-dose Phase</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="5"/>
                <participants group_id="P3" count="5"/>
                <participants group_id="P4" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="5"/>
                <participants group_id="P3" count="5"/>
                <participants group_id="P4" count="5"/>
              </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>
          <title>Multiple-dose Phase</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="5"/>
                <participants group_id="P3" count="5"/>
                <participants group_id="P4" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="5"/>
                <participants group_id="P3" count="5"/>
                <participants group_id="P4" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Two participant were discontinued in Single-dose phase, and other two participants were added in Multiple-dose phase.</population>
      <group_list>
        <group group_id="B1">
          <title>Placebo</title>
          <description>Placebo: ・Single-dose phase: 3steps (low dose, middle dose or high dose group), 2 patients/step, single oral administration after meals&#xD;
・Multiple-dose phase: 3 steps (low dose, middle dose or high dose group), 2 patients/step (the same patients between single- and multiple-dose phases), repeated oral administration for 7 days, BID after meals</description>
        </group>
        <group group_id="B2">
          <title>TAS-205 Low Dose</title>
          <description>TAS-205: ・Single-dose phase: 3 steps (low dose, middle dose or high dose group), 5 patients/step, single oral administration after meals&#xD;
・Multiple-dose phase: 3 steps (low dose, middle dose or high dose group), 5 patients/step (the same patients between single- and multiple-dose phases), repeated oral administration for 7 days, BID after meals</description>
        </group>
        <group group_id="B3">
          <title>TAS-205 Middle Dose</title>
          <description>TAS-205: ・Single-dose phase: 3 steps (low dose, middle dose or high dose group), 5 patients/step, single oral administration after meals&#xD;
・Multiple-dose phase: 3 steps (low dose, middle dose or high dose group), 5 patients/step (the same patients between single- and multiple-dose phases), repeated oral administration for 7 days, BID after meals</description>
        </group>
        <group group_id="B4">
          <title>TAS-205 High Dose</title>
          <description>TAS-205: ・Single-dose phase: 3 steps (low dose, middle dose or high dose group), 5 patients/step, single oral administration after meals&#xD;
・Multiple-dose phase: 3 steps (low dose, middle dose or high dose group), 5 patients/step (the same patients between single- and multiple-dose phases), repeated oral administration for 7 days, BID after meals</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="6"/>
            <count group_id="B2" value="6"/>
            <count group_id="B3" value="5"/>
            <count group_id="B4" value="6"/>
            <count group_id="B5" value="23"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="6"/>
                    <measurement group_id="B5" value="23"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </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_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="5"/>
                    <measurement group_id="B4" value="6"/>
                    <measurement group_id="B5" value="23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Japan</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="6"/>
                    <measurement group_id="B5" value="23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Incidence of Adverse Events</title>
        <description>Source Vocabulary Name for Table Default: CTCAE (4.03)</description>
        <time_frame>From the first administration day to the end of the observation period (ie. single-dose phase: 8 days, multiple-doses phase: 14 days)</time_frame>
        <population>About repeated-dose period, one participants of placebo group and one of TAS-205 high dose group were excluded from analysis population, due to significant deviation from the protocol.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Placebo: ・Single-dose phase: 3steps (low dose, middle dose or high dose group), 2 patients/step, single oral administration after meals&#xD;
・Multiple-dose phase: 3 steps (low dose, middle dose or high dose group), 2 patients/step (the same patients between single- and multiple-dose phases), repeated oral administration for 7 days, BID after meals</description>
          </group>
          <group group_id="O2">
            <title>TAS-205 Low Dose</title>
            <description>TAS-205: ・Single-dose phase: 3 steps (low dose, middle dose or high dose group), 5 patients/step, single oral administration after meals&#xD;
・Multiple-dose phase: 3 steps (low dose, middle dose or high dose group), 5 patients/step (the same patients between single- and multiple-dose phases), repeated oral administration for 7 days, BID after meals</description>
          </group>
          <group group_id="O3">
            <title>TAS-205 Middle Dose</title>
            <description>TAS-205: ・Single-dose phase: 3 steps (low dose, middle dose or high dose group), 5 patients/step, single oral administration after meals&#xD;
・Multiple-dose phase: 3 steps (low dose, middle dose or high dose group), 5 patients/step (the same patients between single- and multiple-dose phases), repeated oral administration for 7 days, BID after meals</description>
          </group>
          <group group_id="O4">
            <title>TAS-205 High Dose</title>
            <description>TAS-205: ・Single-dose phase: 3 steps (low dose, middle dose or high dose group), 5 patients/step, single oral administration after meals&#xD;
・Multiple-dose phase: 3 steps (low dose, middle dose or high dose group), 5 patients/step (the same patients between single- and multiple-dose phases), repeated oral administration for 7 days, BID after meals</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence of Adverse Events</title>
          <description>Source Vocabulary Name for Table Default: CTCAE (4.03)</description>
          <population>About repeated-dose period, one participants of placebo group and one of TAS-205 high dose group were excluded from analysis population, due to significant deviation from the protocol.</population>
          <units>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="5"/>
                <count group_id="O4" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Single-dose Period</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="6"/>
                    <count group_id="O3" value="5"/>
                    <count group_id="O4" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Repeated-dose Period</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                    <count group_id="O2" value="5"/>
                    <count group_id="O3" value="5"/>
                    <count group_id="O4" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="3"/>
                    <measurement group_id="O4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Peak Plasma Concentration (Cmax) of TAS-205</title>
        <description>Due to inspection missing, some data were not analyzed.</description>
        <time_frame>Single-dose phase: immediately before dosing, 0, 0.5, 1, 2, 4, 8, 24, 48 hours post-dose, Multiple-dose phase: Days 1 and 7, immediately before morning dose, 0.5, 1, 2, 4, and 8 hours post-dose and Day 4, immediately before morning dose.</time_frame>
        <population>About repeated-dose period, one participants of TAS-205 high dose group was excluded from analysis population, due to significant deviation from the protocol.</population>
        <group_list>
          <group group_id="O1">
            <title>TAS-205 Low Dose</title>
            <description>TAS-205: ・Single-dose phase: 3 steps (low dose, middle dose or high dose group), 5 patients/step, single oral administration after meals&#xD;
・Multiple-dose phase: 3 steps (low dose, middle dose or high dose group), 5 patients/step (the same patients between single- and multiple-dose phases), repeated oral administration for 7 days, BID after meals</description>
          </group>
          <group group_id="O2">
            <title>TAS-205 Middle Dose</title>
            <description>TAS-205: ・Single-dose phase: 3 steps (low dose, middle dose or high dose group), 5 patients/step, single oral administration after meals&#xD;
・Multiple-dose phase: 3 steps (low dose, middle dose or high dose group), 5 patients/step (the same patients between single- and multiple-dose phases), repeated oral administration for 7 days, BID after meals</description>
          </group>
          <group group_id="O3">
            <title>TAS-205 High Dose</title>
            <description>TAS-205: ・Single-dose phase: 3 steps (low dose, middle dose or high dose group), 5 patients/step, single oral administration after meals&#xD;
・Multiple-dose phase: 3 steps (low dose, middle dose or high dose group), 5 patients/step (the same patients between single- and multiple-dose phases), repeated oral administration for 7 days, BID after meals</description>
          </group>
        </group_list>
        <measure>
          <title>Peak Plasma Concentration (Cmax) of TAS-205</title>
          <description>Due to inspection missing, some data were not analyzed.</description>
          <population>About repeated-dose period, one participants of TAS-205 high dose group was excluded from analysis population, due to significant deviation from the protocol.</population>
          <units>ng/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="5"/>
                <count group_id="O3" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Single-dose Period</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                    <count group_id="O2" value="5"/>
                    <count group_id="O3" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="839" spread="383"/>
                    <measurement group_id="O2" value="1847" spread="996"/>
                    <measurement group_id="O3" value="3202" spread="1493"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Repeated-dose Period (Day 1)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                    <count group_id="O2" value="5"/>
                    <count group_id="O3" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1004" spread="656"/>
                    <measurement group_id="O2" value="1894" spread="691"/>
                    <measurement group_id="O3" value="2635" spread="2813"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Repeated-dose Period (Day 7)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                    <count group_id="O2" value="5"/>
                    <count group_id="O3" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="891" spread="297"/>
                    <measurement group_id="O2" value="2322" spread="776"/>
                    <measurement group_id="O3" value="4660" spread="3671"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Area Under the Plasma Concentration Versus Time Curve (AUC) of TAS-205</title>
        <description>Due to inspection missing, some data were not analyzed.</description>
        <time_frame>Administration period (ie. single-dose phase: from single administration day to 48 hours after the administration, multiple-dose phase: from the first administration day to 8 hours after the last administration)</time_frame>
        <population>About repeated-dose period, one paticipant of TAS-205 high dose group was excluded from analysis population, due to significant deviation from the protocol.</population>
        <group_list>
          <group group_id="O1">
            <title>TAS-205 Low Dose</title>
            <description>TAS-205: ・Single-dose phase: 3 steps (low dose, middle dose or high dose group), 5 patients/step, single oral administration after meals&#xD;
・Multiple-dose phase: 3 steps (low dose, middle dose or high dose group), 5 patients/step (the same patients between single- and multiple-dose phases), repeated oral administration for 7 days, BID after meals</description>
          </group>
          <group group_id="O2">
            <title>TAS-205 Middle Dose</title>
            <description>TAS-205: ・Single-dose phase: 3 steps (low dose, middle dose or high dose group), 5 patients/step, single oral administration after meals&#xD;
・Multiple-dose phase: 3 steps (low dose, middle dose or high dose group), 5 patients/step (the same patients between single- and multiple-dose phases), repeated oral administration for 7 days, BID after meals</description>
          </group>
          <group group_id="O3">
            <title>TAS-205 High Dose</title>
            <description>TAS-205: ・Single-dose phase: 3 steps (low dose, middle dose or high dose group), 5 patients/step, single oral administration after meals&#xD;
・Multiple-dose phase: 3 steps (low dose, middle dose or high dose group), 5 patients/step (the same patients between single- and multiple-dose phases), repeated oral administration for 7 days, BID after meals</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Plasma Concentration Versus Time Curve (AUC) of TAS-205</title>
          <description>Due to inspection missing, some data were not analyzed.</description>
          <population>About repeated-dose period, one paticipant of TAS-205 high dose group was excluded from analysis population, due to significant deviation from the protocol.</population>
          <units>ng*hr/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="5"/>
                <count group_id="O3" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Single-dose Period</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                    <count group_id="O2" value="5"/>
                    <count group_id="O3" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2604" spread="851"/>
                    <measurement group_id="O2" value="5776" spread="2951"/>
                    <measurement group_id="O3" value="9118" spread="3334"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Repeated-dose Period (Day 1)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                    <count group_id="O2" value="5"/>
                    <count group_id="O3" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2525" spread="1208"/>
                    <measurement group_id="O2" value="5281" spread="2553"/>
                    <measurement group_id="O3" value="6391" spread="4731"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Repeated-dose Period (Day 7)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                    <count group_id="O2" value="3"/>
                    <count group_id="O3" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2642" spread="673"/>
                    <measurement group_id="O2" value="6087" spread="2561"/>
                    <measurement group_id="O3" value="9452" spread="4405"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Urinary Excretion of PD Marker</title>
        <description>Ratio of prostaglandin E2 metabolite / creatinine Due to inspection missing, some data were not analyzed.</description>
        <time_frame>Single-dose: Day -1 before administration, 0-24 hr post-dose, and 24-48 hr post-dose, Multiple-doses: Day -1 before administration, 0 hr after administration on Day 1 and 4 to the following day (Day 2 and 5), and 0-24 hr after administration on Day 7.</time_frame>
        <population>About repeated-dose period, one participants of placebo group and one of TAS-205 high dose group were excluded from analysis population, due to significant deviation from the protocol.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Placebo: ・Single-dose phase: 3steps (low dose, middle dose or high dose group), 2 patients/step, single oral administration after meals&#xD;
・Multiple-dose phase: 3 steps (low dose, middle dose or high dose group), 2 patients/step (the same patients between single- and multiple-dose phases), repeated oral administration for 7 days, BID after meals</description>
          </group>
          <group group_id="O2">
            <title>TAS-205 Low Dose</title>
            <description>TAS-205: ・Single-dose phase: 3 steps (low dose, middle dose or high dose group), 5 patients/step, single oral administration after meals&#xD;
・Multiple-dose phase: 3 steps (low dose, middle dose or high dose group), 5 patients/step (the same patients between single- and multiple-dose phases), repeated oral administration for 7 days, BID after meals</description>
          </group>
          <group group_id="O3">
            <title>TAS-205 Middle Dose</title>
            <description>TAS-205: ・Single-dose phase: 3 steps (low dose, middle dose or high dose group), 5 patients/step, single oral administration after meals&#xD;
・Multiple-dose phase: 3 steps (low dose, middle dose or high dose group), 5 patients/step (the same patients between single- and multiple-dose phases), repeated oral administration for 7 days, BID after meals</description>
          </group>
          <group group_id="O4">
            <title>TAS-205 High Dose</title>
            <description>TAS-205: ・Single-dose phase: 3 steps (low dose, middle dose or high dose group), 5 patients/step, single oral administration after meals&#xD;
・Multiple-dose phase: 3 steps (low dose, middle dose or high dose group), 5 patients/step (the same patients between single- and multiple-dose phases), repeated oral administration for 7 days, BID after meals</description>
          </group>
        </group_list>
        <measure>
          <title>The Urinary Excretion of PD Marker</title>
          <description>Ratio of prostaglandin E2 metabolite / creatinine Due to inspection missing, some data were not analyzed.</description>
          <population>About repeated-dose period, one participants of placebo group and one of TAS-205 high dose group were excluded from analysis population, due to significant deviation from the protocol.</population>
          <units>ratio</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="5"/>
                <count group_id="O3" value="5"/>
                <count group_id="O4" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Single-dose Period</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="5"/>
                    <count group_id="O3" value="5"/>
                    <count group_id="O4" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.05" spread="0.14"/>
                    <measurement group_id="O2" value="0.92" spread="0.28"/>
                    <measurement group_id="O3" value="1.13" spread="0.31"/>
                    <measurement group_id="O4" value="1.26" spread="0.46"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Repeated-dose Period (Day 1)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                    <count group_id="O2" value="5"/>
                    <count group_id="O3" value="5"/>
                    <count group_id="O4" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.22" spread="0.34"/>
                    <measurement group_id="O2" value="1.23" spread="0.33"/>
                    <measurement group_id="O3" value="1.07" spread="0.26"/>
                    <measurement group_id="O4" value="1.26" spread="0.34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Repeated-dose Period (Day 7)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                    <count group_id="O2" value="5"/>
                    <count group_id="O3" value="5"/>
                    <count group_id="O4" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.22" spread="0.46"/>
                    <measurement group_id="O2" value="1.27" spread="0.35"/>
                    <measurement group_id="O3" value="1.27" spread="0.21"/>
                    <measurement group_id="O4" value="0.76" spread="0.17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From the first administration day to the end of the observation period (ie. single-dose phase: 8 days, multiple-doses phase: 14 days)</time_frame>
      <desc>Adverse Events were formed by participants of single-dose period and multiple-dose period.</desc>
      <group_list>
        <group group_id="E1">
          <title>Placebo, Single-dose Phase</title>
          <description>Single-dose phase: 3steps (low dose, middle dose or high dose group), 2 patients/step, single oral administration after meals</description>
        </group>
        <group group_id="E2">
          <title>TAS-205 Low Dose, Single-dose Phase</title>
          <description>Single-dose phase: 3 steps (low dose, middle dose or high dose group), 5 patients/step, single oral administration after meals</description>
        </group>
        <group group_id="E3">
          <title>TAS-205 Middle Dose, Single-dose Phase</title>
          <description>Single-dose phase: 3 steps (low dose, middle dose or high dose group), 5 patients/step, single oral administration after meals</description>
        </group>
        <group group_id="E4">
          <title>TAS-205 High Dose, Single-dose</title>
          <description>Single-dose phase: 3 steps (low dose, middle dose or high dose group), 5 patients/step, single oral administration after meals</description>
        </group>
        <group group_id="E5">
          <title>Placebo, Multiple-dose Phase</title>
          <description>Multiple-dose phase: 3 steps (low dose, middle dose or high dose group), 2 patients/step (the same patients between single- and multiple-dose phases), repeated oral administration for 7 days, BID after meals</description>
        </group>
        <group group_id="E6">
          <title>TAS-205 Low Dose, Multiple-dose Phase</title>
          <description>Multiple-dose phase: 3 steps (low dose, middle dose or high dose group), 5 patients/step (the same patients between single- and multiple-dose phases), repeated oral administration for 7 days, BID after meals</description>
        </group>
        <group group_id="E7">
          <title>TAS-205 Middle Dose, Multiple-dose Phase</title>
          <description>Multiple-dose phase: 3 steps (low dose, middle dose or high dose group), 5 patients/step (the same patients between single- and multiple-dose phases), repeated oral administration for 7 days, BID after meals</description>
        </group>
        <group group_id="E8">
          <title>TAS-205 High Dose, Multiple-dose Phase</title>
          <description>Multiple-dose phase: 3 steps (low dose, middle dose or high dose group), 5 patients/step (the same patients between single- and multiple-dose phases), repeated oral administration for 7 days, BID after meals</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="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="4"/>
              </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="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>CTCAE (4.03)</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="3" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E7" subjects_affected="3" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="1" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Catheter site pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Arthropod sting</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Ligament sprain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Cystatin C increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperuricemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Erythema</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Nail bed bleeding</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </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>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Taiho Pharmaceutical Co., Ltd.</name_or_title>
      <organization>Clinical Trial Registration Contact</organization>
      <email>toiawase@taiho.co.jp</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02246478
org study id: Taiho10053030
nct id: NCT02246478
lead sponsor: 
has dmc: No
The objective of this study is to evaluate the safety and pharmacokinetic of TAS-205 in
      patients with Duchenne Muscular Dystrophy.
Duchenne Muscular Dystrophy (DMD) is the most common fatal genetic disorder diagnosed in
      childhood, affecting approximately 1 in every 3500 lives male births. DMD patients suffer
      from a relentless decline in muscle strength that impairs the ability of walking and
      breathing, resulting in their lives with wheelchairs and loss of upper body function. The
      objective of this study is to evaluate the safety and pharmacokinetic of TAS-205 after single
      and multiple doses in DMD patients. It is also evaluated if TAS-205 affects the urinary
      excretion of pharmacodynamic (PD) marker in DMD patients.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Incidence of Adverse Events
time frame: From the first administration day to the end of the observation period (ie. single-dose phase: 8 days, multiple-doses phase: 14 days)
description: Source Vocabulary Name for Table Default: CTCAE (4.03)
measure: Peak Plasma Concentration (Cmax) of TAS-205
time frame: Single-dose phase: immediately before dosing, 0, 0.5, 1, 2, 4, 8, 24, 48 hours post-dose, Multiple-dose phase: Days 1 and 7, immediately before morning dose, 0.5, 1, 2, 4, and 8 hours post-dose and Day 4, immediately before morning dose.
description: Due to inspection missing, some data were not analyzed.
measure: Area Under the Plasma Concentration Versus Time Curve (AUC) of TAS-205
time frame: Administration period (ie. single-dose phase: from single administration day to 48 hours after the administration, multiple-dose phase: from the first administration day to 8 hours after the last administration)
description: Due to inspection missing, some data were not analyzed.
measure: The Urinary Excretion of PD Marker
time frame: Single-dose: Day -1 before administration, 0-24 hr post-dose, and 24-48 hr post-dose, Multiple-doses: Day -1 before administration, 0 hr after administration on Day 1 and 4 to the following day (Day 2 and 5), and 0-24 hr after administration on Day 7.
description: Ratio of prostaglandin E2 metabolite / creatinine Due to inspection missing, some data were not analyzed.
arm group label: Placebo
arm group type: Placebo Comparator
arm group label: TAS-205 low dose
arm group type: Active Comparator
arm group label: TAS-205 middle dose
arm group type: Active Comparator
arm group label: TAS-205 high dose
arm group type: Active Comparator
intervention type: Drug
intervention name: TAS-205
description: Single-dose phase: 3 steps (low dose, middle dose or high dose group), 5 patients/step, single oral administration after meals
Multiple-dose phase: 3 steps (low dose, middle dose or high dose group), 5 patients/step (the same patients between single- and multiple-dose phases), repeated oral administration for 7 days, BID after meals
arm group label: TAS-205 high dose
arm group label: TAS-205 low dose
arm group label: TAS-205 middle dose
intervention type: Drug
intervention name: Placebo
description: Single-dose phase: 3steps (low dose, middle dose or high dose group), 2 patients/step, single oral administration after meals
Multiple-dose phase: 3 steps (low dose, middle dose or high dose group), 2 patients/step (the same patients between single- and multiple-dose phases), repeated oral administration for 7 days, BID after meals
arm group label: Placebo
criteria: 
gender: Male
minimum age: 5 Years
maximum age: 15 Years
healthy volunteers: No
last name: Taiho Pharmaceutical Co.,Ltd.
role: Study Director
affiliation: Taiho Pharmaceutical Co., Ltd.
facility: 
country: Japan
responsible party type: Sponsor
mesh term: Muscular Dystrophies
mesh term: Muscular Dystrophy, Duchenne
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 