<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/NCT03254108</url>
  </required_header>
  <id_info>
    <org_study_id>263-102-00001</org_study_id>
    <secondary_id>JapicCTI-173676</secondary_id>
    <nct_id>NCT03254108</nct_id>
  </id_info>
  <brief_title>Clinical Pharmacology Trial to Investigate the Dose of OPC-61815 Injection Equivalent to Tolvaptan 15-mg Tablet in Patients With Congestive Heart Failure</brief_title>
  <official_title>A Multicenter, Double-blind, Randomized, Active-controlled, Parallel-group Comparison Clinical Pharmacology Trial to Investigate the Dose of OPC-61815 Injection Equivalent to Tolvaptan 15-mg Tablet in Patients With Congestive Heart Failure</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Otsuka Pharmaceutical Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Otsuka Pharmaceutical Co., Ltd.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The dose for intravenous administration of OPC-61815 achieving tolvaptan exposure equivalent&#xD;
      to that for oral administration of tolvaptan 15-mg tablet will be investigated by&#xD;
      administering OPC-61815 injection 2 to 16mg or tolvaptan 15-mg oral tablet to subjects with&#xD;
      congestive heart failure.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 6, 2017</start_date>
  <completion_date type="Actual">April 24, 2018</completion_date>
  <primary_completion_date type="Actual">April 14, 2018</primary_completion_date>
  <phase>N/A</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>Maximum Plasma Concentration (Cmax) of OPC-41061 on Day 1</measure>
    <time_frame>Baseline, 1, 1.5, 2, 4, 6, 12 24 hours after the start of administration of investigational drug</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Concentration-time Curve From Time Zero to 24 Hours (AUC24h) on Day 1</measure>
    <time_frame>Baseline, 1, 1.5, 2, 4, 6, 12 24 hours after the start of administration of investigational drug</time_frame>
  </primary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">61</enrollment>
  <condition>Congestive Heart Failure</condition>
  <arm_group>
    <arm_group_label>OPC-61815 injection 2mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Once daily for 5 days placebo tablet will be orally administered, followed immediately by intravenous administration of OPC-61815 at 2 mg.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>OPC-61815 injection 4mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Once daily for 5 days placebo tablet will be orally administered, followed immediately by intravenous administration of OPC-61815 at 4 mg.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>OPC-61815 injection 8mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Once daily for 5 days placebo tablet will be orally administered, followed immediately by intravenous administration of OPC-61815 at 8 mg.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>OPC-61815 injection 16mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Once daily for 5 days placebo tablet will be orally administered, followed immediately by intravenous administration of OPC-61815 at 16 mg.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Tolvaptan tablet 15mg</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Once daily for 5 days tolvaptan 15-mg tablet will be orally administered, followed immediately by 1-hour intravenous administration of placebo.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>OPC-61815 injection 2mg</intervention_name>
    <description>Once daily for 5 days placebo tablet will be orally administered, followed immediately by intravenous administration of OPC-61815 at 2 mg.</description>
    <arm_group_label>OPC-61815 injection 2mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>OPC-61815 injection 4mg</intervention_name>
    <description>Once daily for 5 days placebo tablet will be orally administered, followed immediately by intravenous administration of OPC-61815 at 4 mg.</description>
    <arm_group_label>OPC-61815 injection 4mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>OPC-61815 injection 8mg</intervention_name>
    <description>Once daily for 5 days placebo tablet will be orally administered, followed immediately by intravenous administration of OPC-61815 at 8 mg.</description>
    <arm_group_label>OPC-61815 injection 8mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>OPC-61815 injection 16mg</intervention_name>
    <description>Once daily for 5 days placebo tablet will be orally administered, followed immediately by intravenous administration of OPC-61815 at 16 mg.</description>
    <arm_group_label>OPC-61815 injection 16mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tolvaptan tablet 15mg</intervention_name>
    <description>Once daily for 5 days tolvaptan 15-mg tablet will be orally administered, followed immediately by 1-hour intravenous administration of placebo.</description>
    <arm_group_label>Tolvaptan tablet 15mg</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Subjects who are currently on treatment with any of the following diuretics&#xD;
&#xD;
               -  Loop diuretics equivalent to furosemide tablet or fine granules at a dose of 40&#xD;
                  mg/day or higher&#xD;
&#xD;
               -  Concomitant use of a loop diuretic and a thiazide diuretic (including thiazide&#xD;
                  analogs) at any dose&#xD;
&#xD;
               -  Concomitant use of a loop diuretic and an aldosterone antagonist or&#xD;
                  potassium-sparing diuretic agent at any dose&#xD;
&#xD;
          2. Subjects with congestive heart failure in whom lower limb edema, pulmonary congestion,&#xD;
             and/or jugular venous distension due to volume overload is present&#xD;
&#xD;
          3. Subjects who are currently hospitalized or who are able to be hospitalized during the&#xD;
             trial&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Subjects with acute heart failure&#xD;
&#xD;
          2. Subjects with a history of hypersensitivity to any of ingredients of OPC-61815 or&#xD;
             tolvaptan&#xD;
&#xD;
          3. Subjects who are unable to sense thirst or who have difficulty with fluid intake&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Hiroaki Ono</last_name>
    <role>Study Director</role>
    <affiliation>Otsuka Pharmaceutical Co., Ltd.</affiliation>
  </overall_official>
  <location>
    <facility>
      <address>
        <city>Kanto</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Japan</country>
  </location_countries>
  <verification_date>July 2021</verification_date>
  <study_first_submitted>August 16, 2017</study_first_submitted>
  <study_first_submitted_qc>August 16, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 18, 2017</study_first_posted>
  <results_first_submitted>July 8, 2021</results_first_submitted>
  <results_first_submitted_qc>July 8, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">July 28, 2021</results_first_posted>
  <last_update_submitted>July 8, 2021</last_update_submitted>
  <last_update_submitted_qc>July 8, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">July 28, 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>Heart Failure</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tolvaptan</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Anonymized Individual participant data (IPD) that underlie the results of this study will be shared with researchers to achieve aims pre-specified in a methodologically sound research proposal.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_time_frame>Data will be available after marketing approval in global markets, or beginning 1-3 years following article Publication. There is no end date to the availability of the data.</ipd_time_frame>
    <ipd_access_criteria>Otsuka will share data on an Otsuka-owned remotely accessible data sharing platform with Python and R analytical software. Research requests should be directed to clinicaltransparency@Otsuka-us.com.</ipd_access_criteria>
  </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>June 19, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/08/NCT03254108/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>June 21, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/08/NCT03254108/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>A total of 74 subjects were screened for this trial, 13 were screen failures, and 61 were randomly assigned to one of the treatment groups. One subject assigned to the OPC-61815 16-mg group was withdrawn due to dehydration before initiation of the trial drug administration; therefore, 60 subjects received at least 1 dosing of the trial drug.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>OPC-61815 Injection 2mg</title>
          <description>Once daily for 5 days placebo tablet will be orally administered, followed immediately by intravenous administration of OPC-61815 at 2 mg.</description>
        </group>
        <group group_id="P2">
          <title>OPC-61815 Injection 4mg</title>
          <description>Once daily for 5 days placebo tablet will be orally administered, followed immediately by intravenous administration of OPC-61815 at 4 mg.</description>
        </group>
        <group group_id="P3">
          <title>OPC-61815 Injection 8mg</title>
          <description>Once daily for 5 days placebo tablet will be orally administered, followed immediately by intravenous administration of OPC-61815 at 8 mg.</description>
        </group>
        <group group_id="P4">
          <title>OPC-61815 Injection 16mg</title>
          <description>Once daily for 5 days placebo tablet will be orally administered, followed immediately by intravenous administration of OPC-61815 at 16 mg.</description>
        </group>
        <group group_id="P5">
          <title>Tolvaptan Tablet 15mg</title>
          <description>Once daily for 5 days tolvaptan 15-mg tablet will be orally administered, followed immediately by 1-hour intravenous administration of placebo.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="13"/>
                <participants group_id="P2" count="12"/>
                <participants group_id="P3" count="12"/>
                <participants group_id="P4" count="12"/>
                <participants group_id="P5" count="12"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Received Treatment</title>
              <participants_list>
                <participants group_id="P1" count="13"/>
                <participants group_id="P2" count="12"/>
                <participants group_id="P3" count="12"/>
                <participants group_id="P4" count="11"/>
                <participants group_id="P5" count="12"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="13"/>
                <participants group_id="P2" count="10"/>
                <participants group_id="P3" count="12"/>
                <participants group_id="P4" count="11"/>
                <participants group_id="P5" count="9"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="1"/>
                <participants group_id="P5" count="3"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="1"/>
                <participants group_id="P5" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>AST/ALT is increased to 3 times upper limit of normal or higher</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Safety Analysis Set: all subjects treated with the investigational medicinal product (IMP) at least once</population>
      <group_list>
        <group group_id="B1">
          <title>OPC-61815 Injection 2mg</title>
          <description>Once daily for 5 days placebo tablet will be orally administered, followed immediately by intravenous administration of OPC-61815 at 2 mg.</description>
        </group>
        <group group_id="B2">
          <title>OPC-61815 Injection 4mg</title>
          <description>Once daily for 5 days placebo tablet will be orally administered, followed immediately by intravenous administration of OPC-61815 at 4 mg.</description>
        </group>
        <group group_id="B3">
          <title>OPC-61815 Injection 8mg</title>
          <description>Once daily for 5 days placebo tablet will be orally administered, followed immediately by intravenous administration of OPC-61815 at 8 mg.</description>
        </group>
        <group group_id="B4">
          <title>OPC-61815 Injection 16mg</title>
          <description>Once daily for 5 days placebo tablet will be orally administered, followed immediately by intravenous administration of OPC-61815 at 16 mg.</description>
        </group>
        <group group_id="B5">
          <title>Tolvaptan Tablet 15mg</title>
          <description>Once daily for 5 days tolvaptan 15-mg tablet will be orally administered, followed immediately by 1-hour intravenous administration of placebo.</description>
        </group>
        <group group_id="B6">
          <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="13"/>
            <count group_id="B2" value="12"/>
            <count group_id="B3" value="12"/>
            <count group_id="B4" value="11"/>
            <count group_id="B5" value="12"/>
            <count group_id="B6" value="60"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="73.7" spread="9.5"/>
                    <measurement group_id="B2" value="74.5" spread="11.9"/>
                    <measurement group_id="B3" value="72.2" spread="9.9"/>
                    <measurement group_id="B4" value="77.9" spread="3.8"/>
                    <measurement group_id="B5" value="74.8" spread="8.9"/>
                    <measurement group_id="B6" value="74.6" spread="9.1"/>
                  </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="5"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="3"/>
                    <measurement group_id="B5" value="2"/>
                    <measurement group_id="B6" value="19"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="7"/>
                    <measurement group_id="B4" value="8"/>
                    <measurement group_id="B5" value="10"/>
                    <measurement group_id="B6" value="41"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Asian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="12"/>
                    <measurement group_id="B4" value="11"/>
                    <measurement group_id="B5" value="12"/>
                    <measurement group_id="B6" value="60"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Japan</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="12"/>
                    <measurement group_id="B4" value="11"/>
                    <measurement group_id="B5" value="12"/>
                    <measurement group_id="B6" value="60"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Maximum Plasma Concentration (Cmax) of OPC-41061 on Day 1</title>
        <time_frame>Baseline, 1, 1.5, 2, 4, 6, 12 24 hours after the start of administration of investigational drug</time_frame>
        <population>Subjects treated with the IMP at least once and had at least 1 data of primary endpoint after IMP administration</population>
        <group_list>
          <group group_id="O1">
            <title>OPC-61815 Injection 2mg</title>
            <description>Once daily for 5 days placebo tablet will be orally administered, followed immediately by intravenous administration of OPC-61815 at 2 mg.</description>
          </group>
          <group group_id="O2">
            <title>OPC-61815 Injection 4mg</title>
            <description>Once daily for 5 days placebo tablet will be orally administered, followed immediately by intravenous administration of OPC-61815 at 4 mg.</description>
          </group>
          <group group_id="O3">
            <title>OPC-61815 Injection 8mg</title>
            <description>Once daily for 5 days placebo tablet will be orally administered, followed immediately by intravenous administration of OPC-61815 at 8 mg.</description>
          </group>
          <group group_id="O4">
            <title>OPC-61815 Injection 16mg</title>
            <description>Once daily for 5 days placebo tablet will be orally administered, followed immediately by intravenous administration of OPC-61815 at 16 mg.</description>
          </group>
          <group group_id="O5">
            <title>Tolvaptan Tablet 15mg</title>
            <description>Once daily for 5 days tolvaptan 15-mg tablet will be orally administered, followed immediately by 1-hour intravenous administration of placebo.</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Plasma Concentration (Cmax) of OPC-41061 on Day 1</title>
          <population>Subjects treated with the IMP at least once and had at least 1 data of primary endpoint after IMP administration</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="11"/>
                <count group_id="O2" value="12"/>
                <count group_id="O3" value="12"/>
                <count group_id="O4" value="11"/>
                <count group_id="O5" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="41.4" spread="11.4"/>
                    <measurement group_id="O2" value="98.6" spread="43.7"/>
                    <measurement group_id="O3" value="149" spread="61.7"/>
                    <measurement group_id="O4" value="282" spread="96.0"/>
                    <measurement group_id="O5" value="325" spread="194"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Area Under the Concentration-time Curve From Time Zero to 24 Hours (AUC24h) on Day 1</title>
        <time_frame>Baseline, 1, 1.5, 2, 4, 6, 12 24 hours after the start of administration of investigational drug</time_frame>
        <population>Subjects treated with the IMP at least once and had at least 1 data of primary endpoint after IMP administration</population>
        <group_list>
          <group group_id="O1">
            <title>OPC-61815 Injection 2mg</title>
            <description>Once daily for 5 days placebo tablet will be orally administered, followed immediately by intravenous administration of OPC-61815 at 2 mg.</description>
          </group>
          <group group_id="O2">
            <title>OPC-61815 Injection 4mg</title>
            <description>Once daily for 5 days placebo tablet will be orally administered, followed immediately by intravenous administration of OPC-61815 at 4 mg.</description>
          </group>
          <group group_id="O3">
            <title>OPC-61815 Injection 8mg</title>
            <description>Once daily for 5 days placebo tablet will be orally administered, followed immediately by intravenous administration of OPC-61815 at 8 mg.</description>
          </group>
          <group group_id="O4">
            <title>OPC-61815 Injection 16mg</title>
            <description>Once daily for 5 days placebo tablet will be orally administered, followed immediately by intravenous administration of OPC-61815 at 16 mg.</description>
          </group>
          <group group_id="O5">
            <title>Tolvaptan Tablet 15mg</title>
            <description>Once daily for 5 days tolvaptan 15-mg tablet will be orally administered, followed immediately by 1-hour intravenous administration of placebo.</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Concentration-time Curve From Time Zero to 24 Hours (AUC24h) on Day 1</title>
          <population>Subjects treated with the IMP at least once and had at least 1 data of primary endpoint after IMP administration</population>
          <units>ng*h/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="11"/>
                <count group_id="O2" value="12"/>
                <count group_id="O3" value="12"/>
                <count group_id="O4" value="11"/>
                <count group_id="O5" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="356" spread="157"/>
                    <measurement group_id="O2" value="983" spread="563"/>
                    <measurement group_id="O3" value="1340" spread="522"/>
                    <measurement group_id="O4" value="2400" spread="1030"/>
                    <measurement group_id="O5" value="2850" spread="1580"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 15 days</time_frame>
      <desc>Subjects who received at least 1 dose of IMP were included in the safety analysis.</desc>
      <group_list>
        <group group_id="E1">
          <title>OPC-61815 Injection 2mg</title>
          <description>Once daily for 5 days placebo tablet will be orally administered, followed immediately by intravenous administration of OPC-61815 at 2 mg.</description>
        </group>
        <group group_id="E2">
          <title>OPC-61815 Injection 4mg</title>
          <description>Once daily for 5 days placebo tablet will be orally administered, followed immediately by intravenous administration of OPC-61815 at 4 mg.</description>
        </group>
        <group group_id="E3">
          <title>OPC-61815 Injection 8mg</title>
          <description>Once daily for 5 days placebo tablet will be orally administered, followed immediately by intravenous administration of OPC-61815 at 8 mg.</description>
        </group>
        <group group_id="E4">
          <title>OPC-61815 Injection 16mg</title>
          <description>Once daily for 5 days placebo tablet will be orally administered, followed immediately by intravenous administration of OPC-61815 at 16 mg.</description>
        </group>
        <group group_id="E5">
          <title>Tolvaptan Tablet 15mg</title>
          <description>Once daily for 5 days tolvaptan 15-mg tablet will be orally administered, followed immediately by 1-hour intravenous administration of placebo.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA Ver. 21.0</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Endocarditis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA Ver. 21.0</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="8" subjects_at_risk="11"/>
                <counts group_id="E5" subjects_affected="10" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Cardiac failure congestive</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Ventricular tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Dry eye</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Catheter site erythema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Infusion site extravasation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Thirst</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Vessel puncture site reaction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Hepatic congestion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Hepatic function abnormal</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Liver disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Vascular access site pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood creatinine increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Blood potassium increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Blood urea increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Blood uric acid increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Electrocardiogram QT prolonged</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Hyperkalaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Hypernatraemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Hyperuricaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Hypoglycaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Delirium</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Haematuria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Neurogenic bladder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Renal impairment</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Decubitus ulcer</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Dermatitis allergic</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Dermatitis contact</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Petechiae</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Jugular vein distension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Director of Clinical Trials</name_or_title>
      <organization>Otsuka Pharmaceutical Co., LTD.</organization>
      <phone>+81-3-6361-7366</phone>
      <email>CL_OPCJ_RDA_Team@otsuka.jp</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03254108
org study id: 263-102-00001
secondary id: JapicCTI-173676
nct id: NCT03254108
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The dose for intravenous administration of OPC-61815 achieving tolvaptan exposure equivalent
      to that for oral administration of tolvaptan 15-mg tablet will be investigated by
      administering OPC-61815 injection 2 to 16mg or tolvaptan 15-mg oral tablet to subjects with
      congestive heart failure.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Maximum Plasma Concentration (Cmax) of OPC-41061 on Day 1
time frame: Baseline, 1, 1.5, 2, 4, 6, 12 24 hours after the start of administration of investigational drug
measure: Area Under the Concentration-time Curve From Time Zero to 24 Hours (AUC24h) on Day 1
time frame: Baseline, 1, 1.5, 2, 4, 6, 12 24 hours after the start of administration of investigational drug
arm group label: OPC-61815 injection 2mg
arm group type: Experimental
description: Once daily for 5 days placebo tablet will be orally administered, followed immediately by intravenous administration of OPC-61815 at 2 mg.
arm group label: OPC-61815 injection 4mg
arm group type: Experimental
description: Once daily for 5 days placebo tablet will be orally administered, followed immediately by intravenous administration of OPC-61815 at 4 mg.
arm group label: OPC-61815 injection 8mg
arm group type: Experimental
description: Once daily for 5 days placebo tablet will be orally administered, followed immediately by intravenous administration of OPC-61815 at 8 mg.
arm group label: OPC-61815 injection 16mg
arm group type: Experimental
description: Once daily for 5 days placebo tablet will be orally administered, followed immediately by intravenous administration of OPC-61815 at 16 mg.
arm group label: Tolvaptan tablet 15mg
arm group type: Active Comparator
description: Once daily for 5 days tolvaptan 15-mg tablet will be orally administered, followed immediately by 1-hour intravenous administration of placebo.
intervention type: Drug
intervention name: OPC-61815 injection 2mg
description: Once daily for 5 days placebo tablet will be orally administered, followed immediately by intravenous administration of OPC-61815 at 2 mg.
arm group label: OPC-61815 injection 2mg
intervention type: Drug
intervention name: OPC-61815 injection 4mg
description: Once daily for 5 days placebo tablet will be orally administered, followed immediately by intravenous administration of OPC-61815 at 4 mg.
arm group label: OPC-61815 injection 4mg
intervention type: Drug
intervention name: OPC-61815 injection 8mg
description: Once daily for 5 days placebo tablet will be orally administered, followed immediately by intravenous administration of OPC-61815 at 8 mg.
arm group label: OPC-61815 injection 8mg
intervention type: Drug
intervention name: OPC-61815 injection 16mg
description: Once daily for 5 days placebo tablet will be orally administered, followed immediately by intravenous administration of OPC-61815 at 16 mg.
arm group label: OPC-61815 injection 16mg
intervention type: Drug
intervention name: Tolvaptan tablet 15mg
description: Once daily for 5 days tolvaptan 15-mg tablet will be orally administered, followed immediately by 1-hour intravenous administration of placebo.
arm group label: Tolvaptan tablet 15mg
criteria: 
gender: All
minimum age: 20 Years
maximum age: 85 Years
healthy volunteers: No
last name: Hiroaki Ono
role: Study Director
affiliation: Otsuka Pharmaceutical Co., Ltd.
facility: 
country: Japan
responsible party type: Sponsor
mesh term: Heart Failure
mesh term: Tolvaptan
sharing ipd: Yes
ipd description: Anonymized Individual participant data (IPD) that underlie the results of this study will be shared with researchers to achieve aims pre-specified in a methodologically sound research proposal.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd time frame: Data will be available after marketing approval in global markets, or beginning 1-3 years following article Publication. There is no end date to the availability of the data.
ipd access criteria: Otsuka will share data on an Otsuka-owned remotely accessible data sharing platform with Python and R analytical software. Research requests should be directed to clinicaltransparency@Otsuka-us.com.
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 