<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/NCT02994394</url>
  </required_header>
  <id_info>
    <org_study_id>156-102-00136</org_study_id>
    <secondary_id>JapicCTI-163471</secondary_id>
    <nct_id>NCT02994394</nct_id>
  </id_info>
  <brief_title>A Study of OPC-41061 Orally Disintegrating (OD) Tablets Using 2 Different Formulations and 2 Dosing Regimens in Healthy Adult Male Subjects</brief_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>
  </oversight_info>
  <brief_summary>
    <textblock>
      To assess the bioequivalence of OPC-41061 OD tablets and OPC-41061 conventional tablets at 15&#xD;
      and 30 mg in healthy adult male subjects.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 6, 2017</start_date>
  <completion_date type="Actual">February 28, 2017</completion_date>
  <primary_completion_date type="Actual">February 28, 2017</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximum Plasma Concentration (Cmax) of Tolvaptan</measure>
    <time_frame>Pre-dose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 16 hours post-dose</time_frame>
    <description>Blood sampling for plasma tolvaptan concentration before IMP administration and 1, 2, 3, 4, 5, 6, 8, 10, 12, and 16 hours postdose in each period in Cohort 1 and 2 was performed for pharmacokinetic evaluation.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Concentration-time Curve From Time Zero to the Last Observable Concentration at Time t (AUCt) of of Tolvaptan</measure>
    <time_frame>Pre-dose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 16 hours post-dose</time_frame>
    <description>Blood sampling for plasma tolvaptan concentration before IMP administration and 1, 2, 3, 4, 5, 6, 8, 10, 12, and 16 hours postdose in each period in Cohort 1 and 2 was performed for pharmacokinetic evaluation.</description>
  </primary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">84</enrollment>
  <condition>Healthy Adult Male</condition>
  <arm_group>
    <arm_group_label>OPC41061(15 mg) disintegrating tablet with water</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>OPC41061 (15 mg) orally disintegrating tablet is administered with water.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>OPC-41061(15 mg) disintegrating tablet without water</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>OPC41061 (15 mg) orally disintegrating tablet is administered without water.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>OPC-41061(15 mg) conventional tablet with water</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>OPC-41061 (15 mg) conventional tablet is administered with water.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>OPC41061(30 mg) disintegrating tablet with water</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>OPC41061 (30 mg) orally disintegrating tablet is administered with water.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>OPC-41061(30 mg) disintegrating tablet without water</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>OPC41061 (30 mg) orally disintegrating tablet is administered without water.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>OPC-41061(30 mg) conventional tablet with water</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>OPC-41061 (30 mg) conventional tablet is administered with water.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>OPC-41061</intervention_name>
    <arm_group_label>OPC-41061(15 mg) conventional tablet with water</arm_group_label>
    <arm_group_label>OPC-41061(15 mg) disintegrating tablet without water</arm_group_label>
    <arm_group_label>OPC-41061(30 mg) conventional tablet with water</arm_group_label>
    <arm_group_label>OPC-41061(30 mg) disintegrating tablet without water</arm_group_label>
    <arm_group_label>OPC41061(15 mg) disintegrating tablet with water</arm_group_label>
    <arm_group_label>OPC41061(30 mg) disintegrating tablet with water</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Body weight of at least 50.0 kg&#xD;
&#xD;
          -  BMI [body weight in kg / (height in m)2] of at least 17.6 kg/m2 and less than 25.0&#xD;
             kg/m2&#xD;
&#xD;
          -  Judged by the investigator or subinvestigator to be capable of providing written&#xD;
             informed consent prior to the start of any trial-related procedures and capable of&#xD;
             complying with the trial procedures for this study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Judged by the investigator,subinvestigator, or sponsor to have a clinically&#xD;
             significant abnormality in results of the screening examination (including a notable&#xD;
             deviation from the site's standard values) or a medical history that could place the&#xD;
             subject at risk or affect the evaluation of drug absorption, distribution, metabolism,&#xD;
             or excretion&#xD;
&#xD;
          -  History of alcohol or drug dependence or abuse within 2 years prior to the trial&#xD;
&#xD;
          -  History or current infection with hepatitis or acquired immunodeficiency syndrome&#xD;
             (AIDS) or carrier of hepatitis B positive surface antigen (HBsAg), anti-hepatitis C&#xD;
             virus (HCV), human immunodeficiency virus (HIV), or syphilis based on the results of&#xD;
             the Treponema pallidum (TP) antibody test or rapid plasma reagin (RPR) test&#xD;
&#xD;
          -  History of any severe drug allergy&#xD;
&#xD;
          -  Positive results in alcohol screening test or urine drug screening test at time of&#xD;
             screening examination or trial site admission&#xD;
&#xD;
          -  Use of any other investigational medicinal product (IMP) within 120 days prior to&#xD;
             Period 1 IMP administration&#xD;
&#xD;
          -  Consumption of any food or beverage containing St. John's wort within 14 days prior to&#xD;
             Period 1 IMP administration&#xD;
&#xD;
          -  Consumption of any food or beverage containing grapefruit, Seville orange, or star&#xD;
             fruit within 7 days prior to Period 1 IMP administration&#xD;
&#xD;
          -  Judgment by the investigator or subinvestigator that the subject should not&#xD;
             participate in the study for any other reason.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>39 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Hiroaki Ono, Mr</last_name>
    <role>Study Director</role>
    <affiliation>Otsuka Pharmaceutical Co., Ltd.</affiliation>
  </overall_official>
  <location>
    <facility>
      <address>
        <city>Kyusyu Region</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Japan</country>
  </location_countries>
  <verification_date>June 2021</verification_date>
  <study_first_submitted>December 13, 2016</study_first_submitted>
  <study_first_submitted_qc>December 14, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 15, 2016</study_first_posted>
  <results_first_submitted>May 10, 2021</results_first_submitted>
  <results_first_submitted_qc>June 6, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">June 28, 2021</results_first_posted>
  <last_update_submitted>June 6, 2021</last_update_submitted>
  <last_update_submitted_qc>June 6, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">June 28, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tolvaptan</mesh_term>
  </intervention_browse>
  <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>November 25, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/94/NCT02994394/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 9, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/94/NCT02994394/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>This single-center, open-label, randomized, 3-period 3-way, crossover study using 2 different formulations and 2 different dosing regimens investigated bioequivalence between tolvaptan orally disintegrating (OD) and conventional tablets in 84 healthy adult male subjects in 2 cohorts. Bioequivalence between the OD and conventional 15 mg tablets was investigated in Cohort 1. In Cohort 2, bioequivalence between the OD and conventional 30 mg tablets was investigated.</recruitment_details>
      <pre_assignment_details>A total of 84 subjects were divided into 2 cohorts of 42 subjects each. The 42 subjects each in 2 cohorts were randomly assigned to the conventional tablet first group, OD tablet with water first group, or OD tablet without water first group according to the randomization code in a 1:1:1 ratio. Forty subjects in Cohort 1 and 41 subjects in Cohort 2 completed the trial.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Cohort 1: Conventional Tablet, Then OD Tablet Without Water, Then OD Tablet With Water</title>
          <description>Subjects received single oral administration of tolvaptan 15 mg in Cohort 1, conventional or OD tablet, with or without water on each administration day in Period 1, Period 2, and Period 3.&#xD;
A washout period of 72 hours was set from postdose in Period 1 until predose in Period 2 and from postdose in Period 2 until predose in Period 3.</description>
        </group>
        <group group_id="P2">
          <title>Cohort 1: OD Tablet With Water, Then Conventional Tablet, Then OD Tablet Without Water</title>
          <description>Subjects received single oral administration of tolvaptan 15 mg in Cohort 1, conventional or OD tablet, with or without water on each administration day in Period 1, Period 2, and Period 3.&#xD;
A washout period of 72 hours was set from postdose in Period 1 until predose in Period 2 and from postdose in Period 2 until predose in Period 3.</description>
        </group>
        <group group_id="P3">
          <title>Cohort 1: OD Tablet Without Water, Then OD Tablet With Water, Then Conventional Tablet</title>
          <description>Subjects received single oral administration of tolvaptan 15 mg in Cohort 1, conventional or OD tablet, with or without water on each administration day in Period 1, Period 2, and Period 3.&#xD;
A washout period of 72 hours was set from postdose in Period 1 until predose in Period 2 and from postdose in Period 2 until predose in Period 3.</description>
        </group>
        <group group_id="P4">
          <title>Cohort 2: Conventional Tablet, Then OD Tablet Without Water, Then OD Tablet With Water</title>
          <description>Subjects received single oral administration of tolvaptan 30 mg in Cohort 2, conventional or OD tablet, with or without water on each administration day in Period 1, Period 2, and Period 3.&#xD;
A washout period of 72 hours was set from postdose in Period 1 until predose in Period 2 and from postdose in Period 2 until predose in Period 3.</description>
        </group>
        <group group_id="P5">
          <title>Cohort 2: OD Tablet With Water, Then Conventional Tablet, Then OD Tablet Without Water</title>
          <description>Subjects received single oral administration of tolvaptan 30 mg in Cohort 2, conventional or OD tablet, with or without water on each administration day in Period 1, Period 2, and Period 3.&#xD;
A washout period of 72 hours was set from postdose in Period 1 until predose in Period 2 and from postdose in Period 2 until predose in Period 3.</description>
        </group>
        <group group_id="P6">
          <title>Cohort 2: OD Tablet Without Water, Then OD Tablet With Water, Then Conventional Tablet</title>
          <description>Subjects received single oral administration of tolvaptan 30 mg in Cohort 2, conventional or OD tablet, with or without water on each administration day in Period 1, Period 2, and Period 3.&#xD;
A washout period of 72 hours was set from postdose in Period 1 until predose in Period 2 and from postdose in Period 2 until predose in Period 3.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Period 1 (Days 1 to 3)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
                <participants group_id="P2" count="14"/>
                <participants group_id="P3" count="14"/>
                <participants group_id="P4" count="14"/>
                <participants group_id="P5" count="14"/>
                <participants group_id="P6" count="14"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
                <participants group_id="P2" count="14"/>
                <participants group_id="P3" count="13"/>
                <participants group_id="P4" count="14"/>
                <participants group_id="P5" count="14"/>
                <participants group_id="P6" count="14"/>
              </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="1"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Period 2 (Days 4 to 6)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
                <participants group_id="P2" count="14"/>
                <participants group_id="P3" count="13"/>
                <participants group_id="P4" count="14"/>
                <participants group_id="P5" count="14"/>
                <participants group_id="P6" count="14"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
                <participants group_id="P2" count="13"/>
                <participants group_id="P3" count="13"/>
                <participants group_id="P4" count="14"/>
                <participants group_id="P5" count="13"/>
                <participants group_id="P6" count="14"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="1"/>
                <participants group_id="P6" count="0"/>
              </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="1"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="1"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Period 3 (Days 7 and 8)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
                <participants group_id="P2" count="13"/>
                <participants group_id="P3" count="13"/>
                <participants group_id="P4" count="14"/>
                <participants group_id="P5" count="13"/>
                <participants group_id="P6" count="14"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
                <participants group_id="P2" count="13"/>
                <participants group_id="P3" count="13"/>
                <participants group_id="P4" count="14"/>
                <participants group_id="P5" count="13"/>
                <participants group_id="P6" count="14"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Safety analysis set: all subjects that received at least 1 dose of investigational medicinal product (IMP).</population>
      <group_list>
        <group group_id="B1">
          <title>Cohort 1</title>
          <description>Subjects received single oral administration of tolvaptan 15 mg in Cohort 1, conventional or OD tablet, with or without water on each administration day in Period 1, Period 2, and Period 3.&#xD;
A washout period of 72 hours was set from postdose in Period 1 until predose in Period 2 and from postdose in Period 2 until predose in Period 3.</description>
        </group>
        <group group_id="B2">
          <title>Cohort 2</title>
          <description>Subjects received single oral administration of tolvaptan 30 mg in Cohort 2, conventional or OD tablet, with or without water on each administration day in Period 1, Period 2, and Period 3.&#xD;
A washout period of 72 hours was set from postdose in Period 1 until predose in Period 2 and from postdose in Period 2 until predose in Period 3.</description>
        </group>
        <group group_id="B3">
          <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="42"/>
            <count group_id="B2" value="42"/>
            <count group_id="B3" value="84"/>
          </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="24.4" spread="4.3"/>
                    <measurement group_id="B2" value="23.5" spread="4.8"/>
                    <measurement group_id="B3" value="24.0" spread="4.5"/>
                  </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_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="42"/>
                    <measurement group_id="B2" value="42"/>
                    <measurement group_id="B3" value="84"/>
                  </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>Japanese</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="42"/>
                    <measurement group_id="B2" value="42"/>
                    <measurement group_id="B3" value="84"/>
                  </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="42"/>
                    <measurement group_id="B2" value="42"/>
                    <measurement group_id="B3" value="84"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Maximum Plasma Concentration (Cmax) of Tolvaptan</title>
        <description>Blood sampling for plasma tolvaptan concentration before IMP administration and 1, 2, 3, 4, 5, 6, 8, 10, 12, and 16 hours postdose in each period in Cohort 1 and 2 was performed for pharmacokinetic evaluation.</description>
        <time_frame>Pre-dose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 16 hours post-dose</time_frame>
        <population>Bioequivalence analysis set: all subjects with both AUCt and Cmax values across Period 1, Period 2, and Period 3.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1: 15 mg Conventional Tablet</title>
            <description>Single oral administration of 1 tolvaptan 15 mg conventional tablet with water under fasting conditions</description>
          </group>
          <group group_id="O2">
            <title>Cohort 1: 15 mg OD Tablet Without Water</title>
            <description>Single oral administration of 1 tolvaptan 15 mg OD tablet without water under fasting conditions</description>
          </group>
          <group group_id="O3">
            <title>Cohort 1: 15 mg OD Tablet With Water</title>
            <description>Single oral administration of 1 tolvaptan 15 mg OD tablet with water under fasting conditions</description>
          </group>
          <group group_id="O4">
            <title>Cohort 2: 30 mg Conventional Tablet</title>
            <description>Single oral administration of 1 tolvaptan 30 mg conventional tablet with water under fasting conditions</description>
          </group>
          <group group_id="O5">
            <title>Cohort 2: 30 mg OD Tablet Without Water</title>
            <description>Single oral administration of 1 tolvaptan 30 mg OD tablet without water under fasting conditions</description>
          </group>
          <group group_id="O6">
            <title>Cohort 2: 30 mg OD Tablet With Water</title>
            <description>Single oral administration of 1 tolvaptan 30 mg OD tablet with water under fasting conditions</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Plasma Concentration (Cmax) of Tolvaptan</title>
          <description>Blood sampling for plasma tolvaptan concentration before IMP administration and 1, 2, 3, 4, 5, 6, 8, 10, 12, and 16 hours postdose in each period in Cohort 1 and 2 was performed for pharmacokinetic evaluation.</description>
          <population>Bioequivalence analysis set: all subjects with both AUCt and Cmax values across Period 1, Period 2, and Period 3.</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="39"/>
                <count group_id="O2" value="39"/>
                <count group_id="O3" value="39"/>
                <count group_id="O4" value="41"/>
                <count group_id="O5" value="41"/>
                <count group_id="O6" value="41"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="131" spread="71.0"/>
                    <measurement group_id="O2" value="149" spread="72.6"/>
                    <measurement group_id="O3" value="125" spread="63.1"/>
                    <measurement group_id="O4" value="203" spread="72.7"/>
                    <measurement group_id="O5" value="218" spread="56.0"/>
                    <measurement group_id="O6" value="198" spread="54.7"/>
                  </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 the Last Observable Concentration at Time t (AUCt) of of Tolvaptan</title>
        <description>Blood sampling for plasma tolvaptan concentration before IMP administration and 1, 2, 3, 4, 5, 6, 8, 10, 12, and 16 hours postdose in each period in Cohort 1 and 2 was performed for pharmacokinetic evaluation.</description>
        <time_frame>Pre-dose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 16 hours post-dose</time_frame>
        <population>Bioequivalence analysis set: all subjects with both AUCt and Cmax values across Period 1, Period 2, and Period 3.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1: 15 mg Conventional Tablet</title>
            <description>Single oral administration of 1 tolvaptan 15 mg conventional tablet with water under fasting conditions</description>
          </group>
          <group group_id="O2">
            <title>Cohort 1: 15 mg OD Tablet Without Water</title>
            <description>Single oral administration of 1 tolvaptan 15 mg OD tablet without water under fasting conditions</description>
          </group>
          <group group_id="O3">
            <title>Cohort 1: 15 mg OD Tablet With Water</title>
            <description>Single oral administration of 1 tolvaptan 15 mg OD tablet with water under fasting conditions</description>
          </group>
          <group group_id="O4">
            <title>Cohort 2: 30 mg Conventional Tablet</title>
            <description>Single oral administration of 1 tolvaptan 30 mg conventional tablet with water under fasting conditions</description>
          </group>
          <group group_id="O5">
            <title>Cohort 2: 30 mg OD Tablet Without Water</title>
            <description>Single oral administration of 1 tolvaptan 30 mg OD tablet without water under fasting conditions</description>
          </group>
          <group group_id="O6">
            <title>Cohort 2: 30 mg OD Tablet With Water</title>
            <description>Single oral administration of 1 tolvaptan 30 mg OD tablet with water under fasting conditions</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Concentration-time Curve From Time Zero to the Last Observable Concentration at Time t (AUCt) of of Tolvaptan</title>
          <description>Blood sampling for plasma tolvaptan concentration before IMP administration and 1, 2, 3, 4, 5, 6, 8, 10, 12, and 16 hours postdose in each period in Cohort 1 and 2 was performed for pharmacokinetic evaluation.</description>
          <population>Bioequivalence analysis set: all subjects with both AUCt and Cmax values across Period 1, Period 2, and Period 3.</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="39"/>
                <count group_id="O2" value="39"/>
                <count group_id="O3" value="39"/>
                <count group_id="O4" value="41"/>
                <count group_id="O5" value="41"/>
                <count group_id="O6" value="41"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="697" spread="440"/>
                    <measurement group_id="O2" value="674" spread="361"/>
                    <measurement group_id="O3" value="685" spread="392"/>
                    <measurement group_id="O4" value="1120" spread="334"/>
                    <measurement group_id="O5" value="1130" spread="306"/>
                    <measurement group_id="O6" value="1110" spread="312"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Treatment-emergent adverse events were collected during the treatment period (8 days)</time_frame>
      <desc>Safety analysis set: all subjects that received at least 1 dose of IMP.</desc>
      <group_list>
        <group group_id="E1">
          <title>Cohort 1: 15 mg Conventional Tablet</title>
          <description>Single oral administration of 1 tolvaptan 15 mg conventional tablet with water under fasting conditions</description>
        </group>
        <group group_id="E2">
          <title>Cohort 1: 15 mg OD Tablet Without Water</title>
          <description>Single oral administration of 1 tolvaptan 15 mg OD tablet without water under fasting conditions</description>
        </group>
        <group group_id="E3">
          <title>Cohort 1: 15 mg OD Tablet With Water</title>
          <description>Single oral administration of 1 tolvaptan 15 mg OD tablet with water under fasting conditions</description>
        </group>
        <group group_id="E4">
          <title>Cohort 2: 30 mg Conventional Tablet</title>
          <description>Single oral administration of 1 tolvaptan 30 mg conventional tablet with water under fasting conditions</description>
        </group>
        <group group_id="E5">
          <title>Cohort 2: 30 mg OD Tablet Without Water</title>
          <description>Single oral administration of 1 tolvaptan 30 mg OD tablet without water under fasting conditions</description>
        </group>
        <group group_id="E6">
          <title>Cohort 2: 30 mg OD Tablet With Water</title>
          <description>Single oral administration of 1 tolvaptan 30 mg OD tablet with water under fasting conditions</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="41"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="42"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="42"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="42"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="42"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>2</frequency_threshold>
        <default_vocab>MedDRA Ver. 20.0</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="1" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="41"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="41"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="42"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="42"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="41"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="42"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="42"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="41"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="42"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="42"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine Aminotransferase Increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="41"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="42"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="42"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="41"/>
              </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/NCT02994394
org study id: 156-102-00136
secondary id: JapicCTI-163471
nct id: NCT02994394
lead sponsor: 
has dmc: No
To assess the bioequivalence of OPC-41061 OD tablets and OPC-41061 conventional tablets at 15
      and 30 mg in healthy adult male subjects.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum Plasma Concentration (Cmax) of Tolvaptan
time frame: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 16 hours post-dose
description: Blood sampling for plasma tolvaptan concentration before IMP administration and 1, 2, 3, 4, 5, 6, 8, 10, 12, and 16 hours postdose in each period in Cohort 1 and 2 was performed for pharmacokinetic evaluation.
measure: Area Under the Concentration-time Curve From Time Zero to the Last Observable Concentration at Time t (AUCt) of of Tolvaptan
time frame: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 16 hours post-dose
description: Blood sampling for plasma tolvaptan concentration before IMP administration and 1, 2, 3, 4, 5, 6, 8, 10, 12, and 16 hours postdose in each period in Cohort 1 and 2 was performed for pharmacokinetic evaluation.
arm group label: OPC41061(15 mg) disintegrating tablet with water
arm group type: Experimental
description: OPC41061 (15 mg) orally disintegrating tablet is administered with water.
arm group label: OPC-41061(15 mg) disintegrating tablet without water
arm group type: Experimental
description: OPC41061 (15 mg) orally disintegrating tablet is administered without water.
arm group label: OPC-41061(15 mg) conventional tablet with water
arm group type: Experimental
description: OPC-41061 (15 mg) conventional tablet is administered with water.
arm group label: OPC41061(30 mg) disintegrating tablet with water
arm group type: Experimental
description: OPC41061 (30 mg) orally disintegrating tablet is administered with water.
arm group label: OPC-41061(30 mg) disintegrating tablet without water
arm group type: Experimental
description: OPC41061 (30 mg) orally disintegrating tablet is administered without water.
arm group label: OPC-41061(30 mg) conventional tablet with water
arm group type: Experimental
description: OPC-41061 (30 mg) conventional tablet is administered with water.
intervention type: Drug
intervention name: OPC-41061
arm group label: OPC-41061(15 mg) conventional tablet with water
arm group label: OPC-41061(15 mg) disintegrating tablet without water
arm group label: OPC-41061(30 mg) conventional tablet with water
arm group label: OPC-41061(30 mg) disintegrating tablet without water
arm group label: OPC41061(15 mg) disintegrating tablet with water
arm group label: OPC41061(30 mg) disintegrating tablet with water
criteria: 
gender: Male
minimum age: 20 Years
maximum age: 39 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Hiroaki Ono, Mr
role: Study Director
affiliation: Otsuka Pharmaceutical Co., Ltd.
facility: 
country: Japan
responsible party type: Sponsor
mesh term: Tolvaptan
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 