<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/NCT03296787</url>
  </required_header>
  <id_info>
    <org_study_id>TAK-954-1007</org_study_id>
    <secondary_id>U1111-1196-9206</secondary_id>
    <secondary_id>2017-000715-16</secondary_id>
    <nct_id>NCT03296787</nct_id>
  </id_info>
  <brief_title>A Study to Evaluate the Effect of Renal Impairment and Dialysis Treatment on the Pharmacokinetics (PK) of a Single Intravenous (IV) TAK-954</brief_title>
  <official_title>A Phase 1, Open-Label, Parallel Group Trial to Evaluate the Effect of Renal Impairment and Dialysis Treatment on the Pharmacokinetics of a Single Intravenous Dose of TAK-954</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Takeda</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Takeda</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the effect of varying degrees of renal function on&#xD;
      the PK of TAK-954 following single-dose IV administration and to investigate the impact of&#xD;
      hemodialysis on the PK of single IV doses of TAK-954.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The drug being tested in this study is called TAK-954. This study will evaluate the effect of&#xD;
      varying degrees of renal function on the PK of TAK-954 following single-dose IV&#xD;
      administration and to investigate the impact of hemodialysis on the PK of single IV doses of&#xD;
      TAK-954.&#xD;
&#xD;
      The study will enroll approximately up to 40 participants. Participants will be enrolled in&#xD;
      one of the 5 treatment groups based on their renal impairment which will be determined based&#xD;
      on Cockcroft and Gault (CG) equation as follows:&#xD;
&#xD;
        -  Group A TAK-954 0.2 mg: Healthy Participants&#xD;
&#xD;
        -  Group B TAK-954 0.2 mg: Mild Renal Impairment&#xD;
&#xD;
        -  Group C TAK-954 0.2 mg: Moderate Renal Impairment&#xD;
&#xD;
        -  Group D TAK-954 0.2 mg: Severe Renal Impairment or End-stage Renal Disease (ESRD)&#xD;
           Without Hemodialysis&#xD;
&#xD;
        -  Group E TAK-954 0.2 mg: End-stage Renal Disease (ESRD) With Hemodialysis&#xD;
&#xD;
      All participants in groups A to D will receive a single dose of TAK-954 and two single doses&#xD;
      in Group E.&#xD;
&#xD;
      Enrollment in Group B (Mild) and Group E (ESRD requiring dialysis) will be based on&#xD;
      assessment of safety and available PK data from Group C and Group D respectively.&#xD;
&#xD;
      This multi-center trial will be conducted in Czech Republic and Hungary. The overall time to&#xD;
      participate in this study is approximately 8 weeks. Participants in Groups A to D will remain&#xD;
      confined to clinic for 3 days. For both treatments, participants in Group E requiring&#xD;
      dialysis will remain confined to clinic for 3 days. All participants will make a final visit&#xD;
      to the clinic 10-14 days after receiving their last dose for a follow-up assessment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 21, 2017</start_date>
  <completion_date type="Actual">August 9, 2019</completion_date>
  <primary_completion_date type="Actual">August 9, 2019</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Groups A, C and D; Cmax: Maximum Observed Plasma Concentration for TAK-954 (Total and Free)</measure>
    <time_frame>Day 1 pre-infusion and at multiple time points (up to 120 hours) post-infusion</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Groups A, C and D; AUC(0-72): Area Under the Plasma Concentration-time Curve From Time 0 to 72 Hours Post-dose for TAK-954 (Free and Total)</measure>
    <time_frame>Day 1 pre-infusion and at multiple time points (up to 72 hours) post-infusion</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Groups A, C and D; AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-954 (Free and Total)</measure>
    <time_frame>Day 1 pre-infusion and at multiple time points (up to 120 hours) post-infusion</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Groups A, C and D; AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-954 (Free and Total)</measure>
    <time_frame>Day 1 pre-infusion and at multiple time points (up to 120 hours) post-infusion</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Groups A, C and D; Ae: Amount of TAK-954 Excreted in Urine</measure>
    <time_frame>Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Group E; Ae: Amount of TAK-954 Excreted in Urine in Period 1</measure>
    <time_frame>Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Group E; Ae: Amount of TAK-954 Excreted in Urine in Period 2</measure>
    <time_frame>Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Groups A, C and D; Fe: Fraction of TAK-954 Excreted in Urine</measure>
    <time_frame>Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Group E; Fe: Fraction of TAK-954 Excreted in Urine in Period 1</measure>
    <time_frame>Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Group E; Fe: Fraction of TAK-954 Excreted in Urine in Period 2</measure>
    <time_frame>Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Groups A, C and D; CLR: Renal Clearance for TAK-954</measure>
    <time_frame>Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Group E; CLR: Renal Clearance for TAK-954 in Period 1</measure>
    <time_frame>Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Group E; CLR: Renal Clearance for TAK-954 in Period 2</measure>
    <time_frame>Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Group E; CLD: Clearance of Dialysate for TAK-954 in Period 2</measure>
    <time_frame>Day 1 pre-infusion and at multiple time points (up to 4 hours) post-infusion</time_frame>
  </primary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">32</enrollment>
  <condition>Renal Impairment</condition>
  <condition>Healthy Volunteers</condition>
  <arm_group>
    <arm_group_label>Group A TAK-954 0.2 mg: Healthy Participants</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants with normal renal function receive TAK-954 0.2 milligram (mg), infusion, intravenously in fasted state, once on Day 1 of a 6-day period.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group B TAK-954 0.2 mg: Mild Renal Impairment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants receive TAK-954 0.2 mg, infusion, intravenously in fasted state, once on Day 1 of a 6-day period.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group C TAK-954 0.2 mg: Moderate Renal Impairment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants receive TAK-954 0.2 mg, infusion, intravenously in fasted state, once on Day 1 of a 6-day period.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group D TAK-954 0.2 mg: Severe Renal Impairment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants without hemodialysis or End-stage Renal Disease (ESRD) receive TAK-954 0.2 mg, infusion, intravenously in fasted state, once on Day 1 of a 6-day period.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group E TAK-954 0.2 mg: End-stage Renal Disease (ESRD)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants with hemodialysis receive TAK-954 0.2 mg, infusion, intravenously in fasted state, once on Day 1 of a 4-day period followed by a minimum 13-day washout period, further followed by TAK-954 0.2 mg, infusion, intravenously in fasted state, once on Day 1 of a 4-day period.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TAK-954</intervention_name>
    <description>TAK-954 intravenous infusion.</description>
    <arm_group_label>Group A TAK-954 0.2 mg: Healthy Participants</arm_group_label>
    <arm_group_label>Group B TAK-954 0.2 mg: Mild Renal Impairment</arm_group_label>
    <arm_group_label>Group C TAK-954 0.2 mg: Moderate Renal Impairment</arm_group_label>
    <arm_group_label>Group D TAK-954 0.2 mg: Severe Renal Impairment</arm_group_label>
    <arm_group_label>Group E TAK-954 0.2 mg: End-stage Renal Disease (ESRD)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. All participants: Male and female participants (non-childbearing potential) who are&#xD;
             aged 18 to 75 years, inclusive, with a body mass index (BMI) between 18 to 35 kilogram&#xD;
             per square meter (kg/m^2).&#xD;
&#xD;
          2. Group A: As much as possible, the healthy participants with normal renal function&#xD;
             (creatinine clearance [CLcr] greater than or equal to [&gt;=] 90 milliliter per minute&#xD;
             [mL/min]) should be comparable to participants with renal impairment with respect to&#xD;
             median age and weight (approximately 50 percent [%] of healthy participants on each&#xD;
             side of the median age and weight of currently enrolled renally-impaired participants&#xD;
             grouped together), sex, and race. This will be decided by the investigators in&#xD;
             discussion with Takeda.&#xD;
&#xD;
          3. Groups B to E: Participants who have stable RI, defined as no clinically significant&#xD;
             change in disease status, as documented by the participant's most recent CLcr&#xD;
             assessment; serum creatinine must not vary more than approximately 30% from Screening&#xD;
             to Day -1 to confirm stable disease. Participants should also be in good health&#xD;
             commensurate with their renal status.&#xD;
&#xD;
               -  Group B: Participants with mild RI (CLcr 60 to less than [&lt;] 90 mL/min).&#xD;
&#xD;
               -  Group C: Participants with moderate RI (CLcr 30 to &lt;60 mL/min).&#xD;
&#xD;
               -  Group D: Participants with severe RI or ESRD but not requiring dialysis (CLcr &lt;30&#xD;
                  mL/min).&#xD;
&#xD;
               -  Group E: Participants with ESRD requiring dialysis (&lt;15 mL/min requiring&#xD;
                  hemodialysis at least 3 times/week, and having been on the same dialysis&#xD;
                  treatment regimen for at least 1 month before trial entry).&#xD;
&#xD;
          4. Participants should be on a stable drug regimen defined as not starting a new drug or&#xD;
             changing dosage within 7 days or 5 half-lives (whichever is longer) before dosing with&#xD;
             TAK-954.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. All participants:&#xD;
&#xD;
               -  Are renal allograft recipients within 1 year of screening.&#xD;
&#xD;
               -  Have a history of gastrointestinal (GI) motility disorder or intestinal&#xD;
                  obstruction.&#xD;
&#xD;
               -  Have urinary incontinence without catheterization.&#xD;
&#xD;
          2. Group A: Participants who, in the discretion of the investigator, have a history of&#xD;
             clinically significant endocrine, GI, cardiovascular, hematological, hepatic,&#xD;
             immunological, renal, respiratory, genitourinary, or major neurological (including&#xD;
             stroke and chronic seizures) abnormalities or diseases will be excluded from the&#xD;
             trial.&#xD;
&#xD;
          3. Groups B to E:&#xD;
&#xD;
               -  Receive dialysis other than intermittent dialysis (except Group E).&#xD;
&#xD;
               -  Have renal disease secondary to hepatic disease (hepatorenal syndrome).&#xD;
&#xD;
               -  At the discretion of the investigators, have any significant hepatic, cardiac, or&#xD;
                  pulmonary disease or participants who are clinically nephrotic.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Medical Director</last_name>
    <role>Study Director</role>
    <affiliation>Takeda</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>PRA CZ, s.r.o</name>
      <address>
        <city>Praha 7</city>
        <state>Praha</state>
        <zip>170 00</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fakultni Nemocnice Hradec Kralove</name>
      <address>
        <city>Hradec Kralove</city>
        <zip>500 05</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>PRA Magyarorszag Kft.</name>
      <address>
        <city>Budapest</city>
        <zip>1077</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Szent Imre Egyetemi Oktatokorhaz Belgyogyazati Szakmak Matrix Intezet</name>
      <address>
        <city>Budapest</city>
        <zip>1115</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Czechia</country>
    <country>Hungary</country>
  </location_countries>
  <verification_date>August 2020</verification_date>
  <study_first_submitted>September 25, 2017</study_first_submitted>
  <study_first_submitted_qc>September 25, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 28, 2017</study_first_posted>
  <results_first_submitted>August 6, 2020</results_first_submitted>
  <results_first_submitted_qc>August 6, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">August 25, 2020</results_first_posted>
  <last_update_submitted>August 6, 2020</last_update_submitted>
  <last_update_submitted_qc>August 6, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">August 25, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Drug therapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Renal Insufficiency</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Takeda makes patient-level, de-identified data sets and associated documents available for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.</ipd_description>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>October 9, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/87/NCT03296787/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>December 12, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/87/NCT03296787/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants took part in the study at 4 investigative sites in Czech Republic and Hungary from 21 November 2017 to 09 August 2019.</recruitment_details>
      <pre_assignment_details>Participants with normal renal function and renal impairment were enrolled in 1 of the 4 groups: A (healthy), C (moderate), D (severe), and E (end-stage renal disease [ESRD]) to receive TAK-954 0.2 milligram (mg). Based on available safety and pharmacokinetics (PK) data from Group C, participants were not enrolled in Group B (mild).</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Group A: Healthy Participants</title>
          <description>TAK-954 0.2 mg, infusion, intravenously in fasted state, once on Day 1 of a 6-day period (Treatment 1), followed by a minimum 13-day washout period, further followed by probe cocktail of different cytochrome P-450 (CYP) substrates (caffeine 100 mg, oral [CYP1A2] + midazolam 0.025 milligram per kilogram [mg/kg], intravenously [CYP3A4]), once on Day 1 of a 4-day period (Treatment 2) in participants with normal renal function.</description>
        </group>
        <group group_id="P2">
          <title>Group C: Moderate Renal Impairment</title>
          <description>TAK-954 0.2 mg, infusion, intravenously in fasted state, once on Day 1 of a 6-day period (Treatment 1), followed by a minimum 13-day washout period, further followed by probe cocktail of different CYP substrates (caffeine 100 mg, oral [CYP1A2] + midazolam 0.025 mg/kg, intravenously [CYP3A4]), once on Day 1 of a 4-day period (Treatment 2) in participants with moderate renal impairment.</description>
        </group>
        <group group_id="P3">
          <title>Group D: Severe Renal Impairment Not Requiring Dialysis</title>
          <description>TAK-954 0.2 mg, infusion, intravenously in fasted state, once on Day 1 of a 6-day period (Treatment 1) in participants with severe renal impairment or ESRD without dialysis.</description>
        </group>
        <group group_id="P4">
          <title>Group E: ESRD Requiring Dialysis</title>
          <description>TAK-954 0.2 mg, infusion, intravenously in fasted state, 1 hour after the end of dialysis, once on Day 1 of a 6-day Period 1, followed by a minimum 13-day washout period, further followed by TAK-954 0.2 mg, infusion, intravenously in fasted state, 2 hours before the start of dialysis, once on Day 1 of a 4-day Period 2 in participants with ESRD requiring dialysis.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="8"/>
                <participants group_id="P3" count="9"/>
                <participants group_id="P4" count="7"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="8"/>
                <participants group_id="P3" count="9"/>
                <participants group_id="P4" count="7"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The safety set consisted of all participants who were enrolled and received at least 1 dose of trial drug.</population>
      <group_list>
        <group group_id="B1">
          <title>Group A: Healthy Participants</title>
          <description>TAK-954 0.2 mg, infusion, intravenously in fasted state, once on Day 1 of a 6-day period (Treatment 1), followed by a minimum 13-day washout period, further followed by probe cocktail of different cytochrome P-450 (CYP) substrates (caffeine 100 mg, oral [CYP1A2] + midazolam 0.025 milligram per kilogram [mg/kg], intravenously [CYP3A4]), once on Day 1 of a 4-day period (Treatment 2) in participants with normal renal function.</description>
        </group>
        <group group_id="B2">
          <title>Group C: Moderate Renal Impairment</title>
          <description>TAK-954 0.2 mg, infusion, intravenously in fasted state, once on Day 1 of a 6-day period (Treatment 1), followed by a minimum 13-day washout period, further followed by probe cocktail of different CYP substrates (caffeine 100 mg, oral [CYP1A2] + midazolam 0.025 mg/kg, intravenously [CYP3A4]), once on Day 1 of a 4-day period (Treatment 2) in participants with moderate renal impairment.</description>
        </group>
        <group group_id="B3">
          <title>Group D: Severe Renal Impairment Not Requiring Dialysis</title>
          <description>TAK-954 0.2 mg, infusion, intravenously in fasted state, once on Day 1 of a 6-day period (Treatment 1) in participants with severe renal impairment or ESRD without dialysis.</description>
        </group>
        <group group_id="B4">
          <title>Group E: ESRD Requiring Dialysis</title>
          <description>TAK-954 0.2 mg, infusion, intravenously in fasted state, 1 hour after the end of dialysis, once on Day 1 of a 6-day Period 1, followed by a minimum 13-day washout period, further followed by TAK-954 0.2 mg, infusion, intravenously in fasted state, 2 hours before the start of dialysis, once on Day 1 of a 4-day Period 2 in participants with ESRD requiring dialysis.</description>
        </group>
        <group group_id="B5">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="8"/>
            <count group_id="B2" value="8"/>
            <count group_id="B3" value="9"/>
            <count group_id="B4" value="7"/>
            <count group_id="B5" value="32"/>
          </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="57.0" spread="15.62"/>
                    <measurement group_id="B2" value="70.6" spread="3.50"/>
                    <measurement group_id="B3" value="62.2" spread="11.03"/>
                    <measurement group_id="B4" value="52.6" spread="10.06"/>
                    <measurement group_id="B5" value="60.9" spread="12.38"/>
                  </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="3"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</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="7"/>
                    <measurement group_id="B5" value="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="9"/>
                    <measurement group_id="B4" value="7"/>
                    <measurement group_id="B5" value="32"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="9"/>
                    <measurement group_id="B4" value="7"/>
                    <measurement group_id="B5" value="32"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Czech Republic</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="3"/>
                    <measurement group_id="B5" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hungary</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="4"/>
                    <measurement group_id="B5" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Weight</title>
          <units>kilogram (kg)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="79.95" spread="7.773"/>
                    <measurement group_id="B2" value="75.95" spread="13.035"/>
                    <measurement group_id="B3" value="76.22" spread="14.457"/>
                    <measurement group_id="B4" value="82.39" spread="7.006"/>
                    <measurement group_id="B5" value="78.43" spread="11.072"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Body Mass Index (BMI)</title>
          <units>kilogram per square meter (kg/m^2)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="26.88" spread="4.051"/>
                    <measurement group_id="B2" value="26.25" spread="4.166"/>
                    <measurement group_id="B3" value="27.33" spread="4.272"/>
                    <measurement group_id="B4" value="28.14" spread="2.673"/>
                    <measurement group_id="B5" value="27.13" spread="3.765"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Height</title>
          <units>centimeter (cm)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="173.25" spread="9.706"/>
                    <measurement group_id="B2" value="170.25" spread="9.543"/>
                    <measurement group_id="B3" value="166.89" spread="9.519"/>
                    <measurement group_id="B4" value="171.00" spread="6.976"/>
                    <measurement group_id="B5" value="170.22" spread="8.965"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Creatine Clearance</title>
          <units>milliliter per minute (mL/min)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="107.11" spread="23.417"/>
                    <measurement group_id="B2" value="46.20" spread="10.767"/>
                    <measurement group_id="B3" value="23.20" spread="6.385"/>
                    <measurement group_id="B4" value="10.54" spread="2.504"/>
                    <measurement group_id="B5" value="47.16" spread="39.484"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Estimated Glomerular Filtration Rate (eGFR)</title>
          <units>milliliter per minute/1.73 square meter</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="89.93" spread="13.779"/>
                    <measurement group_id="B2" value="41.68" spread="11.527"/>
                    <measurement group_id="B3" value="18.13" spread="8.648"/>
                    <measurement group_id="B4" value="6.93" spread="2.757"/>
                    <measurement group_id="B5" value="39.52" spread="33.514"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Groups A, C and D; Cmax: Maximum Observed Plasma Concentration for TAK-954 (Total and Free)</title>
        <time_frame>Day 1 pre-infusion and at multiple time points (up to 120 hours) post-infusion</time_frame>
        <population>The PK set consisted of all participants who were enrolled and received at least 1 dose of trial drug and had at least 1 measurable TAK-954 plasma concentration. The outcome measure (OM) was planned to be assessed for the groups where blood samples were collected before the start of TAK-954 infusion and through 120 hours post-infusion.</population>
        <group_list>
          <group group_id="O1">
            <title>Group A: Healthy Participants</title>
            <description>TAK-954 0.2 mg, infusion, intravenously in fasted state, once on Day 1 of a 6-day period (Treatment 1), followed by a minimum 13-day washout period, further followed by probe cocktail of different cytochrome P-450 (CYP) substrates (caffeine 100 mg, oral [CYP1A2] + midazolam 0.025 milligram per kilogram [mg/kg], intravenously [CYP3A4]), once on Day 1 of a 4-day period (Treatment 2) in participants with normal renal function.</description>
          </group>
          <group group_id="O2">
            <title>Group C: Moderate Renal Impairment</title>
            <description>TAK-954 0.2 mg, infusion, intravenously in fasted state, once on Day 1 of a 6-day period (Treatment 1), followed by a minimum 13-day washout period, further followed by probe cocktail of different CYP substrates (caffeine 100 mg, oral [CYP1A2] + midazolam 0.025 mg/kg, intravenously [CYP3A4]), once on Day 1 of a 4-day period (Treatment 2) in participants with moderate renal impairment.</description>
          </group>
          <group group_id="O3">
            <title>Group D: Severe Renal Impairment Not Requiring Dialysis</title>
            <description>TAK-954 0.2 mg, infusion, intravenously in fasted state, once on Day 1 of a 6-day period (Treatment 1) in participants with severe renal impairment or ESRD without dialysis.</description>
          </group>
        </group_list>
        <measure>
          <title>Groups A, C and D; Cmax: Maximum Observed Plasma Concentration for TAK-954 (Total and Free)</title>
          <population>The PK set consisted of all participants who were enrolled and received at least 1 dose of trial drug and had at least 1 measurable TAK-954 plasma concentration. The outcome measure (OM) was planned to be assessed for the groups where blood samples were collected before the start of TAK-954 infusion and through 120 hours post-infusion.</population>
          <units>nanogram per milliliter (ng/mL)</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="8"/>
                <count group_id="O3" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>TAK-954 (Total)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.623" spread="12.8"/>
                    <measurement group_id="O2" value="2.536" spread="23.2"/>
                    <measurement group_id="O3" value="2.660" spread="17.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TAK-954 (Free)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.1270" spread="29.2"/>
                    <measurement group_id="O2" value="0.1282" spread="22.5"/>
                    <measurement group_id="O3" value="0.1572" spread="21.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>TAK-954 (Total): An analysis of variance (ANOVA) were performed on log transformed Cmax (total TAK-954) to compare moderate renal impairment group with the normal renal function group.</non_inferiority_desc>
            <p_value>0.7265</p_value>
            <method>ANOVA</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>TAK-954 (Total): An ANOVA were performed on log transformed Cmax (total TAK-954) to compare severe renal impairment group with the normal renal function group.</non_inferiority_desc>
            <p_value>0.9839</p_value>
            <method>ANOVA</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>TAK-954 (Free): An ANOVA were performed on natural logarithm of Cmax (free TAK-954) to compare moderate renal impairment group with the normal renal function group.</non_inferiority_desc>
            <p_value>0.9393</p_value>
            <method>ANOVA</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>TAK-954 (Free): An ANOVA were performed on natural logarithm of Cmax (free TAK-954) to compare severe renal impairment group with the normal renal function group.</non_inferiority_desc>
            <p_value>0.1321</p_value>
            <method>ANOVA</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Groups A, C and D; AUC(0-72): Area Under the Plasma Concentration-time Curve From Time 0 to 72 Hours Post-dose for TAK-954 (Free and Total)</title>
        <time_frame>Day 1 pre-infusion and at multiple time points (up to 72 hours) post-infusion</time_frame>
        <population>The PK set consisted of all participants who were enrolled and received at least 1 dose of trial drug and had at least 1 measurable TAK-954 plasma concentration. The OM was planned to be assessed for the groups where blood samples were collected before the start of TAK-954 infusion and through 120 hours post-infusion.</population>
        <group_list>
          <group group_id="O1">
            <title>Group A: Healthy Participants</title>
            <description>TAK-954 0.2 mg, infusion, intravenously in fasted state, once on Day 1 of a 6-day period (Treatment 1), followed by a minimum 13-day washout period, further followed by probe cocktail of different cytochrome P-450 (CYP) substrates (caffeine 100 mg, oral [CYP1A2] + midazolam 0.025 milligram per kilogram [mg/kg], intravenously [CYP3A4]), once on Day 1 of a 4-day period (Treatment 2) in participants with normal renal function.</description>
          </group>
          <group group_id="O2">
            <title>Group C: Moderate Renal Impairment</title>
            <description>TAK-954 0.2 mg, infusion, intravenously in fasted state, once on Day 1 of a 6-day period (Treatment 1), followed by a minimum 13-day washout period, further followed by probe cocktail of different CYP substrates (caffeine 100 mg, oral [CYP1A2] + midazolam 0.025 mg/kg, intravenously [CYP3A4]), once on Day 1 of a 4-day period (Treatment 2) in participants with moderate renal impairment.</description>
          </group>
          <group group_id="O3">
            <title>Group D: Severe Renal Impairment Not Requiring Dialysis</title>
            <description>TAK-954 0.2 mg, infusion, intravenously in fasted state, once on Day 1 of a 6-day period (Treatment 1) in participants with severe renal impairment or ESRD without dialysis.</description>
          </group>
        </group_list>
        <measure>
          <title>Groups A, C and D; AUC(0-72): Area Under the Plasma Concentration-time Curve From Time 0 to 72 Hours Post-dose for TAK-954 (Free and Total)</title>
          <population>The PK set consisted of all participants who were enrolled and received at least 1 dose of trial drug and had at least 1 measurable TAK-954 plasma concentration. The OM was planned to be assessed for the groups where blood samples were collected before the start of TAK-954 infusion and through 120 hours post-infusion.</population>
          <units>hour*nanogram per milliliter (h*ng/mL)</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="8"/>
                <count group_id="O3" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>TAK-954 (Total)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22.25" spread="19.1"/>
                    <measurement group_id="O2" value="24.91" spread="22.9"/>
                    <measurement group_id="O3" value="28.62" spread="18.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TAK-954 (Free)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.078" spread="25.7"/>
                    <measurement group_id="O2" value="1.259" spread="25.1"/>
                    <measurement group_id="O3" value="1.690" spread="25.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>TAK-954 (Total): An ANOVA were performed on log transformed AUC(0-72) (total TAK-954) to compare moderate renal impairment group with the normal renal function group.</non_inferiority_desc>
            <p_value>0.3600</p_value>
            <method>ANOVA</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>TAK-954 (Total): An ANOVA were performed on log transformed AUC(0-72) (total TAK-954) to compare severe renal impairment group with the normal renal function group.</non_inferiority_desc>
            <p_value>0.0816</p_value>
            <method>ANOVA</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>TAK-954 (Free): An ANOVA were performed on natural logarithm of AUC(0-72) (free TAK-954) to compare moderate renal impairment group with the normal renal function group.</non_inferiority_desc>
            <p_value>0.2686</p_value>
            <method>ANOVA</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>TAK-954 (Free): An ANOVA were performed on natural logarithm of AUC(0-72) (free TAK-954) to compare severe renal impairment group with the normal renal function group.</non_inferiority_desc>
            <p_value>0.0059</p_value>
            <method>ANOVA</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Groups A, C and D; AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-954 (Free and Total)</title>
        <time_frame>Day 1 pre-infusion and at multiple time points (up to 120 hours) post-infusion</time_frame>
        <population>The PK set consisted of all participants who were enrolled and received at least 1 dose of trial drug and had at least 1 measurable TAK-954 plasma concentration. The OM was planned to be assessed for the groups where blood samples were collected before the start of TAK-954 infusion and through 120 hours post-infusion.</population>
        <group_list>
          <group group_id="O1">
            <title>Group A: Healthy Participants</title>
            <description>TAK-954 0.2 mg, infusion, intravenously in fasted state, once on Day 1 of a 6-day period (Treatment 1), followed by a minimum 13-day washout period, further followed by probe cocktail of different cytochrome P-450 (CYP) substrates (caffeine 100 mg, oral [CYP1A2] + midazolam 0.025 milligram per kilogram [mg/kg], intravenously [CYP3A4]), once on Day 1 of a 4-day period (Treatment 2) in participants with normal renal function.</description>
          </group>
          <group group_id="O2">
            <title>Group C: Moderate Renal Impairment</title>
            <description>TAK-954 0.2 mg, infusion, intravenously in fasted state, once on Day 1 of a 6-day period (Treatment 1), followed by a minimum 13-day washout period, further followed by probe cocktail of different CYP substrates (caffeine 100 mg, oral [CYP1A2] + midazolam 0.025 mg/kg, intravenously [CYP3A4]), once on Day 1 of a 4-day period (Treatment 2) in participants with moderate renal impairment.</description>
          </group>
          <group group_id="O3">
            <title>Group D: Severe Renal Impairment Not Requiring Dialysis</title>
            <description>TAK-954 0.2 mg, infusion, intravenously in fasted state, once on Day 1 of a 6-day period (Treatment 1) in participants with severe renal impairment or ESRD without dialysis.</description>
          </group>
        </group_list>
        <measure>
          <title>Groups A, C and D; AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-954 (Free and Total)</title>
          <population>The PK set consisted of all participants who were enrolled and received at least 1 dose of trial drug and had at least 1 measurable TAK-954 plasma concentration. The OM was planned to be assessed for the groups where blood samples were collected before the start of TAK-954 infusion and through 120 hours post-infusion.</population>
          <units>h*ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="8"/>
                <count group_id="O3" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>TAK-954 (Total)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="24.39" spread="17.7"/>
                    <measurement group_id="O2" value="30.00" spread="20.0"/>
                    <measurement group_id="O3" value="34.28" spread="19.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TAK-954 (Free)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.184" spread="26.8"/>
                    <measurement group_id="O2" value="1.516" spread="24.3"/>
                    <measurement group_id="O3" value="2.025" spread="26.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>TAK-954 (Total): An ANOVA were performed on log transformed AUClast (total TAK-954) to compare moderate renal impairment group with the normal renal function group.</non_inferiority_desc>
            <p_value>0.0998</p_value>
            <method>ANOVA</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>TAK-954 (Total): An ANOVA were performed on log transformed AUClast (total TAK-954) to compare severe renal impairment group with the normal renal function group.</non_inferiority_desc>
            <p_value>0.0155</p_value>
            <method>ANOVA</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>TAK-954 (Free): An ANOVA were performed on natural logarithm of AUClast (free TAK-954) to compare moderate renal impairment group with the normal renal function group.</non_inferiority_desc>
            <p_value>0.0916</p_value>
            <method>ANOVA</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>TAK-954 (Free): An ANOVA were performed on natural logarithm of AUClast (free TAK-954) to compare severe renal impairment group with the normal renal function group.</non_inferiority_desc>
            <p_value>0.0014</p_value>
            <method>ANOVA</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Groups A, C and D; AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-954 (Free and Total)</title>
        <time_frame>Day 1 pre-infusion and at multiple time points (up to 120 hours) post-infusion</time_frame>
        <population>PK set:participants who enrolled and received at least 1 dose of trial drug and had at least 1 measurable TAK-954 plasma concentration. Here,&quot;overall number of participants analyzed&quot;: participants who were evaluable for this OM. OM was planned to be assessed in groups where blood samples collected pre-TAK-954 infusion up to 120 hours post-infusion.</population>
        <group_list>
          <group group_id="O1">
            <title>Group A: Healthy Participants</title>
            <description>TAK-954 0.2 mg, infusion, intravenously in fasted state, once on Day 1 of a 6-day period (Treatment 1), followed by a minimum 13-day washout period, further followed by probe cocktail of different cytochrome P-450 (CYP) substrates (caffeine 100 mg, oral [CYP1A2] + midazolam 0.025 milligram per kilogram [mg/kg], intravenously [CYP3A4]), once on Day 1 of a 4-day period (Treatment 2) in participants with normal renal function.</description>
          </group>
          <group group_id="O2">
            <title>Group C: Moderate Renal Impairment</title>
            <description>TAK-954 0.2 mg, infusion, intravenously in fasted state, once on Day 1 of a 6-day period (Treatment 1), followed by a minimum 13-day washout period, further followed by probe cocktail of different CYP substrates (caffeine 100 mg, oral [CYP1A2] + midazolam 0.025 mg/kg, intravenously [CYP3A4]), once on Day 1 of a 4-day period (Treatment 2) in participants with moderate renal impairment.</description>
          </group>
          <group group_id="O3">
            <title>Group D: Severe Renal Impairment Not Requiring Dialysis</title>
            <description>TAK-954 0.2 mg, infusion, intravenously in fasted state, once on Day 1 of a 6-day period (Treatment 1) in participants with severe renal impairment or ESRD without dialysis.</description>
          </group>
        </group_list>
        <measure>
          <title>Groups A, C and D; AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-954 (Free and Total)</title>
          <population>PK set:participants who enrolled and received at least 1 dose of trial drug and had at least 1 measurable TAK-954 plasma concentration. Here,&quot;overall number of participants analyzed&quot;: participants who were evaluable for this OM. OM was planned to be assessed in groups where blood samples collected pre-TAK-954 infusion up to 120 hours post-infusion.</population>
          <units>h*ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="7"/>
                <count group_id="O3" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>TAK-954 (Total)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25.43" spread="16.8"/>
                    <measurement group_id="O2" value="34.90" spread="16.2"/>
                    <measurement group_id="O3" value="38.59" spread="23.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TAK-954 (Free)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.234" spread="28.4"/>
                    <measurement group_id="O2" value="1.749" spread="24.8"/>
                    <measurement group_id="O3" value="2.320" spread="29.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>TAK-954 (Total): An ANOVA were performed on log transformed AUC∞ (total TAK-954) to compare moderate renal impairment group with the normal renal function group.</non_inferiority_desc>
            <p_value>0.0038</p_value>
            <method>ANOVA</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>TAK-954 (Total): An ANOVA were performed on log transformed AUC∞ (total TAK-954) to compare severe renal impairment group with the normal renal function group.</non_inferiority_desc>
            <p_value>0.0004</p_value>
            <method>ANOVA</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>TAK-954 (Free): An ANOVA were performed on natural logarithm of AUC∞ (free TAK-954) to compare moderate renal impairment group with the normal renal function group.</non_inferiority_desc>
            <p_value>0.0389</p_value>
            <method>ANOVA</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>TAK-954 (Free): An ANOVA were performed on natural logarithm of AUC∞ (free TAK-954) to compare severe renal impairment group with the normal renal function group.</non_inferiority_desc>
            <p_value>0.0011</p_value>
            <method>ANOVA</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Groups A, C and D; Ae: Amount of TAK-954 Excreted in Urine</title>
        <time_frame>Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion</time_frame>
        <population>The PK set consisted of all participants who were enrolled and received at least 1 dose of trial drug and had at least 1 measurable TAK-954 plasma concentration.</population>
        <group_list>
          <group group_id="O1">
            <title>Group A: Healthy Participants</title>
            <description>TAK-954 0.2 mg, infusion, intravenously in fasted state, once on Day 1 of a 6-day period (Treatment 1), followed by a minimum 13-day washout period, further followed by probe cocktail of different cytochrome P-450 (CYP) substrates (caffeine 100 mg, oral [CYP1A2] + midazolam 0.025 milligram per kilogram [mg/kg], intravenously [CYP3A4]), once on Day 1 of a 4-day period (Treatment 2) in participants with normal renal function.</description>
          </group>
          <group group_id="O2">
            <title>Group C: Moderate Renal Impairment</title>
            <description>TAK-954 0.2 mg, infusion, intravenously in fasted state, once on Day 1 of a 6-day period (Treatment 1), followed by a minimum 13-day washout period, further followed by probe cocktail of different CYP substrates (caffeine 100 mg, oral [CYP1A2] + midazolam 0.025 mg/kg, intravenously [CYP3A4]), once on Day 1 of a 4-day period (Treatment 2) in participants with moderate renal impairment.</description>
          </group>
          <group group_id="O3">
            <title>Group D: Severe Renal Impairment Not Requiring Dialysis</title>
            <description>TAK-954 0.2 mg, infusion, intravenously in fasted state, once on Day 1 of a 6-day period (Treatment 1) in participants with severe renal impairment or ESRD without dialysis.</description>
          </group>
        </group_list>
        <measure>
          <title>Groups A, C and D; Ae: Amount of TAK-954 Excreted in Urine</title>
          <population>The PK set consisted of all participants who were enrolled and received at least 1 dose of trial drug and had at least 1 measurable TAK-954 plasma concentration.</population>
          <units>milligram (mg)</units>
          <param>Geometric Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="8"/>
                <count group_id="O3" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.03797" spread="0.011633"/>
                    <measurement group_id="O2" value="0.01763" spread="0.0087713"/>
                    <measurement group_id="O3" value="0.01190" spread="0.0091124"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Group E; Ae: Amount of TAK-954 Excreted in Urine in Period 1</title>
        <time_frame>Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion</time_frame>
        <population>The PK set consisted of all participants who were enrolled and received at least 1 dose of trial drug and had at least 1 measurable TAK-954 plasma concentration. Here, &quot;overall number of participants analyzed&quot; are the participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Group E: ESRD Requiring Dialysis</title>
            <description>TAK-954 0.2 mg, infusion, intravenously in fasted state, 1 hour after the end of dialysis, once on Day 1 of a 6-day Period 1, followed by a minimum 13-day washout period, further followed by TAK-954 0.2 mg, infusion, intravenously in fasted state, 2 hours before the start of dialysis, once on Day 1 of a 4-day Period 2 in participants with ESRD requiring dialysis.</description>
          </group>
        </group_list>
        <measure>
          <title>Group E; Ae: Amount of TAK-954 Excreted in Urine in Period 1</title>
          <population>The PK set consisted of all participants who were enrolled and received at least 1 dose of trial drug and had at least 1 measurable TAK-954 plasma concentration. Here, &quot;overall number of participants analyzed&quot; are the participants who were evaluable for this outcome measure.</population>
          <units>mg</units>
          <param>Geometric Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0003489" spread="0.00021788"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Group E; Ae: Amount of TAK-954 Excreted in Urine in Period 2</title>
        <time_frame>Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion</time_frame>
        <population>The PK set consisted of all participants who were enrolled and received at least 1 dose of trial drug and had at least 1 measurable TAK-954 plasma concentration. Here, &quot;overall number of participants analyzed&quot; are the participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Group E: ESRD Requiring Dialysis</title>
            <description>TAK-954 0.2 mg, infusion, intravenously in fasted state, 1 hour after the end of dialysis, once on Day 1 of a 6-day Period 1, followed by a minimum 13-day washout period, further followed by TAK-954 0.2 mg, infusion, intravenously in fasted state, 2 hours before the start of dialysis, once on Day 1 of a 4-day Period 2 in participants with ESRD requiring dialysis.</description>
          </group>
        </group_list>
        <measure>
          <title>Group E; Ae: Amount of TAK-954 Excreted in Urine in Period 2</title>
          <population>The PK set consisted of all participants who were enrolled and received at least 1 dose of trial drug and had at least 1 measurable TAK-954 plasma concentration. Here, &quot;overall number of participants analyzed&quot; are the participants who were evaluable for this outcome measure.</population>
          <units>mg</units>
          <param>Geometric Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.001240" spread="0.00062000"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Groups A, C and D; Fe: Fraction of TAK-954 Excreted in Urine</title>
        <time_frame>Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion</time_frame>
        <population>The PK set consisted of all participants who were enrolled and received at least 1 dose of trial drug and had at least 1 measurable TAK-954 plasma concentration.</population>
        <group_list>
          <group group_id="O1">
            <title>Group A: Healthy Participants</title>
            <description>TAK-954 0.2 mg, infusion, intravenously in fasted state, once on Day 1 of a 6-day period (Treatment 1), followed by a minimum 13-day washout period, further followed by probe cocktail of different cytochrome P-450 (CYP) substrates (caffeine 100 mg, oral [CYP1A2] + midazolam 0.025 milligram per kilogram [mg/kg], intravenously [CYP3A4]), once on Day 1 of a 4-day period (Treatment 2) in participants with normal renal function.</description>
          </group>
          <group group_id="O2">
            <title>Group C: Moderate Renal Impairment</title>
            <description>TAK-954 0.2 mg, infusion, intravenously in fasted state, once on Day 1 of a 6-day period (Treatment 1), followed by a minimum 13-day washout period, further followed by probe cocktail of different CYP substrates (caffeine 100 mg, oral [CYP1A2] + midazolam 0.025 mg/kg, intravenously [CYP3A4]), once on Day 1 of a 4-day period (Treatment 2) in participants with moderate renal impairment.</description>
          </group>
          <group group_id="O3">
            <title>Group D: Severe Renal Impairment Not Requiring Dialysis</title>
            <description>TAK-954 0.2 mg, infusion, intravenously in fasted state, once on Day 1 of a 6-day period (Treatment 1) in participants with severe renal impairment or ESRD without dialysis.</description>
          </group>
        </group_list>
        <measure>
          <title>Groups A, C and D; Fe: Fraction of TAK-954 Excreted in Urine</title>
          <population>The PK set consisted of all participants who were enrolled and received at least 1 dose of trial drug and had at least 1 measurable TAK-954 plasma concentration.</population>
          <units>percentage of TAK-954 dose</units>
          <param>Geometric Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="8"/>
                <count group_id="O3" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19.00" spread="5.8075"/>
                    <measurement group_id="O2" value="8.808" spread="4.3746"/>
                    <measurement group_id="O3" value="5.953" spread="4.5595"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Group E; Fe: Fraction of TAK-954 Excreted in Urine in Period 1</title>
        <time_frame>Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion</time_frame>
        <population>The PK set consisted of all participants who were enrolled and received at least 1 dose of trial drug and had at least 1 measurable TAK-954 plasma concentration. Here, &quot;overall number of participants analyzed&quot; are the participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Group E: ESRD Requiring Dialysis</title>
            <description>TAK-954 0.2 mg, infusion, intravenously in fasted state, 1 hour after the end of dialysis, once on Day 1 of a 6-day Period 1, followed by a minimum 13-day washout period, further followed by TAK-954 0.2 mg, infusion, intravenously in fasted state, 2 hours before the start of dialysis, once on Day 1 of a 4-day Period 2 in participants with ESRD requiring dialysis.</description>
          </group>
        </group_list>
        <measure>
          <title>Group E; Fe: Fraction of TAK-954 Excreted in Urine in Period 1</title>
          <population>The PK set consisted of all participants who were enrolled and received at least 1 dose of trial drug and had at least 1 measurable TAK-954 plasma concentration. Here, &quot;overall number of participants analyzed&quot; are the participants who were evaluable for this outcome measure.</population>
          <units>percentage of TAK-954 dose</units>
          <param>Geometric Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.1739" spread="0.10869"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Group E; Fe: Fraction of TAK-954 Excreted in Urine in Period 2</title>
        <time_frame>Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion</time_frame>
        <population>The PK set consisted of all participants who were enrolled and received at least 1 dose of trial drug and had at least 1 measurable TAK-954 plasma concentration. Here, &quot;overall number of participants analyzed&quot; are the participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Group E: ESRD Requiring Dialysis</title>
            <description>TAK-954 0.2 mg, infusion, intravenously in fasted state, 1 hour after the end of dialysis, once on Day 1 of a 6-day Period 1, followed by a minimum 13-day washout period, further followed by TAK-954 0.2 mg, infusion, intravenously in fasted state, 2 hours before the start of dialysis, once on Day 1 of a 4-day Period 2 in participants with ESRD requiring dialysis.</description>
          </group>
        </group_list>
        <measure>
          <title>Group E; Fe: Fraction of TAK-954 Excreted in Urine in Period 2</title>
          <population>The PK set consisted of all participants who were enrolled and received at least 1 dose of trial drug and had at least 1 measurable TAK-954 plasma concentration. Here, &quot;overall number of participants analyzed&quot; are the participants who were evaluable for this outcome measure.</population>
          <units>percentage of TAK-954 dose</units>
          <param>Geometric Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.6190" spread="0.30950"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Groups A, C and D; CLR: Renal Clearance for TAK-954</title>
        <time_frame>Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion</time_frame>
        <population>The PK set consisted of all participants who were enrolled and received at least 1 dose of study drug and had at least 1 measurable TAK-954 plasma concentration.</population>
        <group_list>
          <group group_id="O1">
            <title>Group A: Healthy Participants</title>
            <description>TAK-954 0.2 mg, infusion, intravenously in fasted state, once on Day 1 of a 6-day period (Treatment 1), followed by a minimum 13-day washout period, further followed by probe cocktail of different cytochrome P-450 (CYP) substrates (caffeine 100 mg, oral [CYP1A2] + midazolam 0.025 milligram per kilogram [mg/kg], intravenously [CYP3A4]), once on Day 1 of a 4-day period (Treatment 2) in participants with normal renal function.</description>
          </group>
          <group group_id="O2">
            <title>Group C: Moderate Renal Impairment</title>
            <description>TAK-954 0.2 mg, infusion, intravenously in fasted state, once on Day 1 of a 6-day period (Treatment 1), followed by a minimum 13-day washout period, further followed by probe cocktail of different CYP substrates (caffeine 100 mg, oral [CYP1A2] + midazolam 0.025 mg/kg, intravenously [CYP3A4]), once on Day 1 of a 4-day period (Treatment 2) in participants with moderate renal impairment.</description>
          </group>
          <group group_id="O3">
            <title>Group D: Severe Renal Impairment Not Requiring Dialysis</title>
            <description>TAK-954 0.2 mg, infusion, intravenously in fasted state, once on Day 1 of a 6-day period (Treatment 1) in participants with severe renal impairment or ESRD without dialysis.</description>
          </group>
        </group_list>
        <measure>
          <title>Groups A, C and D; CLR: Renal Clearance for TAK-954</title>
          <population>The PK set consisted of all participants who were enrolled and received at least 1 dose of study drug and had at least 1 measurable TAK-954 plasma concentration.</population>
          <units>liter per hour (L/h)</units>
          <param>Geometric Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="8"/>
                <count group_id="O3" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.629" spread="0.78762"/>
                    <measurement group_id="O2" value="1.255" spread="0.51478"/>
                    <measurement group_id="O3" value="0.6836" spread="0.56141"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Group E; CLR: Renal Clearance for TAK-954 in Period 1</title>
        <time_frame>Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion</time_frame>
        <population>The PK set consisted of all participants who were enrolled and received at least 1 dose of trial drug and had at least 1 measurable TAK-954 plasma concentration. Here, &quot;overall number of participants analyzed&quot; are the participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Group E: ESRD Requiring Dialysis</title>
            <description>TAK-954 0.2 mg, infusion, intravenously in fasted state, 1 hour after the end of dialysis, once on Day 1 of a 6-day Period 1, followed by a minimum 13-day washout period, further followed by TAK-954 0.2 mg, infusion, intravenously in fasted state, 2 hours before the start of dialysis, once on Day 1 of a 4-day Period 2 in participants with ESRD requiring dialysis.</description>
          </group>
        </group_list>
        <measure>
          <title>Group E; CLR: Renal Clearance for TAK-954 in Period 1</title>
          <population>The PK set consisted of all participants who were enrolled and received at least 1 dose of trial drug and had at least 1 measurable TAK-954 plasma concentration. Here, &quot;overall number of participants analyzed&quot; are the participants who were evaluable for this outcome measure.</population>
          <units>L/h</units>
          <param>Geometric Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.03192" spread="0.017670"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Group E; CLR: Renal Clearance for TAK-954 in Period 2</title>
        <time_frame>Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion</time_frame>
        <population>The PK set consisted of all participants who were enrolled and received at least 1 dose of trial drug and had at least 1 measurable TAK-954 plasma concentration. Here, &quot;overall number of participants analyzed&quot; are the participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Group E: ESRD Requiring Dialysis</title>
            <description>TAK-954 0.2 mg, infusion, intravenously in fasted state, 1 hour after the end of dialysis, once on Day 1 of a 6-day Period 1, followed by a minimum 13-day washout period, further followed by TAK-954 0.2 mg, infusion, intravenously in fasted state, 2 hours before the start of dialysis, once on Day 1 of a 4-day Period 2 in participants with ESRD requiring dialysis.</description>
          </group>
        </group_list>
        <measure>
          <title>Group E; CLR: Renal Clearance for TAK-954 in Period 2</title>
          <population>The PK set consisted of all participants who were enrolled and received at least 1 dose of trial drug and had at least 1 measurable TAK-954 plasma concentration. Here, &quot;overall number of participants analyzed&quot; are the participants who were evaluable for this outcome measure.</population>
          <units>L/h</units>
          <param>Geometric Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.08330" spread="0.041650"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Group E; CLD: Clearance of Dialysate for TAK-954 in Period 2</title>
        <time_frame>Day 1 pre-infusion and at multiple time points (up to 4 hours) post-infusion</time_frame>
        <population>The PK set consisted of all participants who were enrolled and received at least 1 dose of trial drug and had at least 1 measurable TAK-954 plasma concentration.</population>
        <group_list>
          <group group_id="O1">
            <title>Group E: ESRD Requiring Dialysis</title>
            <description>TAK-954 0.2 mg, infusion, intravenously in fasted state, 1 hour after the end of dialysis, once on Day 1 of a 6-day Period 1, followed by a minimum 13-day washout period, further followed by TAK-954 0.2 mg, infusion, intravenously in fasted state, 2 hours before the start of dialysis, once on Day 1 of a 4-day Period 2 in participants with ESRD requiring dialysis.</description>
          </group>
        </group_list>
        <measure>
          <title>Group E; CLD: Clearance of Dialysate for TAK-954 in Period 2</title>
          <population>The PK set consisted of all participants who were enrolled and received at least 1 dose of trial drug and had at least 1 measurable TAK-954 plasma concentration.</population>
          <units>L/h</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.368" spread="30.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Treatment emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 14 days after the last dose of study drug as Treatment 2 (up to Day 29) in Group A, C, and E), and Treatment 1 (up to Day 15) in for Group D</time_frame>
      <desc>At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. TEAEs includes adverse events occurred during Treatments 1 and 2 in Groups A and C, as planned.</desc>
      <group_list>
        <group group_id="E1">
          <title>Group A: Healthy Participants</title>
          <description>TAK-954 0.2 mg, infusion, intravenously in fasted state, once on Day 1 of a 6-day period (Treatment 1), followed by a minimum 13-day washout period, further followed by probe cocktail of different cytochrome P-450 (CYP) substrates (caffeine 100 mg, oral [CYP1A2] + midazolam 0.025 milligram per kilogram [mg/kg], intravenously [CYP3A4]), once on Day 1 of a 4-day period (Treatment 2) in participants with normal renal function.</description>
        </group>
        <group group_id="E2">
          <title>Group C: Moderate Renal Impairment</title>
          <description>TAK-954 0.2 mg, infusion, intravenously in fasted state, once on Day 1 of a 6-day period (Treatment 1), followed by a minimum 13-day washout period, further followed by probe cocktail of different CYP substrates (caffeine 100 mg, oral [CYP1A2] + midazolam 0.025 mg/kg, intravenously [CYP3A4]), once on Day 1 of a 4-day period (Treatment 2) in participants with moderate renal impairment.</description>
        </group>
        <group group_id="E3">
          <title>Group D: Severe Renal Impairment Not Requiring Dialysis</title>
          <description>TAK-954 0.2 mg, infusion, intravenously in fasted state, once on Day 1 of a 6-day period (Treatment 1) in participants with severe renal impairment or ESRD without dialysis.</description>
        </group>
        <group group_id="E4">
          <title>Group E: ESRD 1 Hour After Dialysis</title>
          <description>TAK-954 0.2 mg, infusion, intravenously in fasted state, 1 hour after the end of dialysis, once on Day 1 of a 6-day Period 1 in participants with ESRD requiring dialysis.</description>
        </group>
        <group group_id="E5">
          <title>Group E: ESRD 2 Hours Before Dialysis</title>
          <description>TAK-954 0.2 mg, infusion, intravenously in fasted state, 2 hours before the start of dialysis, once on Day 1 of a 4-day Period 2 in participants with ESRD requiring dialysis.</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="8"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA 21.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Depressed level of consciousness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>Research Organization shall not publish any articles or papers nor make any presentations, nor assist any other person in publishing any articles or papers or in making any presentations relating or referring to the Study or any results, data or insights from or any data, information or materials obtained or generated in the performance of its obligations without the prior written consent of Takeda, which consent may be granted or withheld in Takeda's sole discretion.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Medical Director</name_or_title>
      <organization>Takeda</organization>
      <phone>+1-877-825-3327</phone>
      <email>trialdisclosures@takeda.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03296787
org study id: TAK-954-1007
secondary id: U1111-1196-9206
secondary id: 2017-000715-16
nct id: NCT03296787
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to evaluate the effect of varying degrees of renal function on
      the PK of TAK-954 following single-dose IV administration and to investigate the impact of
      hemodialysis on the PK of single IV doses of TAK-954.
The drug being tested in this study is called TAK-954. This study will evaluate the effect of
      varying degrees of renal function on the PK of TAK-954 following single-dose IV
      administration and to investigate the impact of hemodialysis on the PK of single IV doses of
      TAK-954.

      The study will enroll approximately up to 40 participants. Participants will be enrolled in
      one of the 5 treatment groups based on their renal impairment which will be determined based
      on Cockcroft and Gault (CG) equation as follows:

        -  Group A TAK-954 0.2 mg: Healthy Participants

        -  Group B TAK-954 0.2 mg: Mild Renal Impairment

        -  Group C TAK-954 0.2 mg: Moderate Renal Impairment

        -  Group D TAK-954 0.2 mg: Severe Renal Impairment or End-stage Renal Disease (ESRD)
           Without Hemodialysis

        -  Group E TAK-954 0.2 mg: End-stage Renal Disease (ESRD) With Hemodialysis

      All participants in groups A to D will receive a single dose of TAK-954 and two single doses
      in Group E.

      Enrollment in Group B (Mild) and Group E (ESRD requiring dialysis) will be based on
      assessment of safety and available PK data from Group C and Group D respectively.

      This multi-center trial will be conducted in Czech Republic and Hungary. The overall time to
      participate in this study is approximately 8 weeks. Participants in Groups A to D will remain
      confined to clinic for 3 days. For both treatments, participants in Group E requiring
      dialysis will remain confined to clinic for 3 days. All participants will make a final visit
      to the clinic 10-14 days after receiving their last dose for a follow-up assessment.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: None (Open Label)
measure: Groups A, C and D; Cmax: Maximum Observed Plasma Concentration for TAK-954 (Total and Free)
time frame: Day 1 pre-infusion and at multiple time points (up to 120 hours) post-infusion
measure: Groups A, C and D; AUC(0-72): Area Under the Plasma Concentration-time Curve From Time 0 to 72 Hours Post-dose for TAK-954 (Free and Total)
time frame: Day 1 pre-infusion and at multiple time points (up to 72 hours) post-infusion
measure: Groups A, C and D; AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-954 (Free and Total)
time frame: Day 1 pre-infusion and at multiple time points (up to 120 hours) post-infusion
measure: Groups A, C and D; AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-954 (Free and Total)
time frame: Day 1 pre-infusion and at multiple time points (up to 120 hours) post-infusion
measure: Groups A, C and D; Ae: Amount of TAK-954 Excreted in Urine
time frame: Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion
measure: Group E; Ae: Amount of TAK-954 Excreted in Urine in Period 1
time frame: Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion
measure: Group E; Ae: Amount of TAK-954 Excreted in Urine in Period 2
time frame: Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion
measure: Groups A, C and D; Fe: Fraction of TAK-954 Excreted in Urine
time frame: Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion
measure: Group E; Fe: Fraction of TAK-954 Excreted in Urine in Period 1
time frame: Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion
measure: Group E; Fe: Fraction of TAK-954 Excreted in Urine in Period 2
time frame: Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion
measure: Groups A, C and D; CLR: Renal Clearance for TAK-954
time frame: Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion
measure: Group E; CLR: Renal Clearance for TAK-954 in Period 1
time frame: Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion
measure: Group E; CLR: Renal Clearance for TAK-954 in Period 2
time frame: Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion
measure: Group E; CLD: Clearance of Dialysate for TAK-954 in Period 2
time frame: Day 1 pre-infusion and at multiple time points (up to 4 hours) post-infusion
arm group label: Group A TAK-954 0.2 mg: Healthy Participants
arm group type: Experimental
description: Participants with normal renal function receive TAK-954 0.2 milligram (mg), infusion, intravenously in fasted state, once on Day 1 of a 6-day period.
arm group label: Group B TAK-954 0.2 mg: Mild Renal Impairment
arm group type: Experimental
description: Participants receive TAK-954 0.2 mg, infusion, intravenously in fasted state, once on Day 1 of a 6-day period.
arm group label: Group C TAK-954 0.2 mg: Moderate Renal Impairment
arm group type: Experimental
description: Participants receive TAK-954 0.2 mg, infusion, intravenously in fasted state, once on Day 1 of a 6-day period.
arm group label: Group D TAK-954 0.2 mg: Severe Renal Impairment
arm group type: Experimental
description: Participants without hemodialysis or End-stage Renal Disease (ESRD) receive TAK-954 0.2 mg, infusion, intravenously in fasted state, once on Day 1 of a 6-day period.
arm group label: Group E TAK-954 0.2 mg: End-stage Renal Disease (ESRD)
arm group type: Experimental
description: Participants with hemodialysis receive TAK-954 0.2 mg, infusion, intravenously in fasted state, once on Day 1 of a 4-day period followed by a minimum 13-day washout period, further followed by TAK-954 0.2 mg, infusion, intravenously in fasted state, once on Day 1 of a 4-day period.
intervention type: Drug
intervention name: TAK-954
description: TAK-954 intravenous infusion.
arm group label: Group A TAK-954 0.2 mg: Healthy Participants
arm group label: Group B TAK-954 0.2 mg: Mild Renal Impairment
arm group label: Group C TAK-954 0.2 mg: Moderate Renal Impairment
arm group label: Group D TAK-954 0.2 mg: Severe Renal Impairment
arm group label: Group E TAK-954 0.2 mg: End-stage Renal Disease (ESRD)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Medical Director
role: Study Director
affiliation: Takeda
facility: 
facility: 
facility: 
facility: 
country: Czechia
country: Hungary
responsible party type: Sponsor
mesh term: Renal Insufficiency
sharing ipd: Yes
ipd description: Takeda makes patient-level, de-identified data sets and associated documents available for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 