<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/NCT03238651</url>
  </required_header>
  <id_info>
    <org_study_id>C34007</org_study_id>
    <secondary_id>U1111-1186-6838</secondary_id>
    <nct_id>NCT03238651</nct_id>
  </id_info>
  <brief_title>A Study of TAK-659 as a Single Agent in Adult East Asian Participants With Non-Hodgkin Lymphoma (NHL)</brief_title>
  <official_title>A Phase 1, Open-label Study of TAK-659 as a Single Agent in Adult East Asian Patients With Non-Hodgkin Lymphoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Calithera Biosciences, Inc</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Calithera Biosciences, Inc</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine the safety, tolerability, maximum tolerated dose&#xD;
      (MTD) and/or recommended phase 2 dose (RP2D) of TAK-659 when administered in East Asian&#xD;
      participants with NHL who do not have an effective standard treatment available and to&#xD;
      characterize the plasma and urine pharmacokinetic (PK) of TAK-659 in East Asian participants&#xD;
      with NHL.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The drug being tested in this study is called TAK-659. TAK-659 is being tested to treat&#xD;
      people who have NHL or people who have relapsed and/or refractory NHL. This study will assess&#xD;
      the safety, tolerability, PK, and preliminary efficacy of single-agent TAK-659 in East Asian&#xD;
      participants with NHL.&#xD;
&#xD;
      The study will enroll approximately 33 to 47 participants, including at least 6 Japanese at&#xD;
      RP2D dose level. Participants will be assigned to one of the following treatment groups:&#xD;
&#xD;
      Dose Escalation Part: TAK-659 Expansion Part: TAK-659 RP2D&#xD;
&#xD;
      This multi-center trial will be conducted in Japan and Republic of Korea. The maximum&#xD;
      duration of participation in dose escalation part of the study is up to 12 months, unless in&#xD;
      the opinion of the investigator and sponsor the participant would derive benefit from&#xD;
      continued therapy beyond 12 months. In expansion part, participants who stop treatment for&#xD;
      any other reason other than PD will continue to have PFS follow-up at the site every 2 months&#xD;
      from the last dose of study drug up to 6 months or until PD. Participants will be followed 28&#xD;
      days after last dose of study drug or until the start of subsequent antineoplastic therapy,&#xD;
      whichever occurs first, for a follow up assessment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Termination of the study by the sponsor due to business decision.&#xD;
  </why_stopped>
  <start_date type="Actual">August 1, 2017</start_date>
  <completion_date type="Actual">August 17, 2020</completion_date>
  <primary_completion_date type="Actual">August 17, 2020</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>Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)</measure>
    <time_frame>From first dose of study drug up to 28 days after the last dose of study drug or before the start of subsequent anticancer therapy (up to Cycle 31) (Cycle length =28 days)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of Participants With Grade 3 or Higher TEAEs</measure>
    <time_frame>From first dose of study drug up to 28 days after the last dose of study drug or before the start of subsequent anticancer therapy (up to Cycle 31) (Cycle length =28 days)</time_frame>
    <description>TEAEs were graded as per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03. As per the NCI-CTCAE, Grade 1 (mild, asymptomatic or mild symptoms); Grade 2 (moderate, minimal, local or noninvasive intervention indicated); Grade 3 (severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated); Grade 4 (life-threatening consequences, urgent intervention indicated); Grade 5 (death related to adverse event [AE]).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of Participants With Serious TEAEs</measure>
    <time_frame>From first dose of study drug up to 28 days after the last dose of study drug or before the start of subsequent anticancer therapy (up to Cycle 31) (Cycle length =28 days)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Dose Escalation Part: Percentage of Participants With Dose-limiting Toxicities (DLTs) During Cycle 1</measure>
    <time_frame>Cycle 1 (Cycle length =28 days)</time_frame>
    <description>DLT was evaluated as per NCI-CTCAE, v4.03 and defined as any of the following events occurring during Cycle 1 that were considered by the investigator to be possibly related to therapy: Grade 4 neutropenia unresolved to less than or equal to (&lt;=) Grade 1 or baseline for more than 7 days in the absence of growth factor support; greater than or equal to (&gt;=) Grade 3 neutropenia with fever and/or infection;Grade 4 thrombocytopenia unresolved to &lt;=Grade 1 or baseline for more than 7 days; &gt;=Grade 3 thrombocytopenia with clinically significant bleeding; Grade &gt;=3 nonhematologic toxicity except for treated &gt;=Grade 3 nausea and/or emesis and diarrhea resolved to less than (&lt;) Grade 3 within 3 days, Grade 3 fatigue &lt;=72 hours, isolated asymptomatic &gt;=Grade 3 laboratory abnormalities resolved to &lt;=Grade 1 or baseline in &lt;=7 days;received &lt;75% of planned doses of study drug in Cycle 1;TAK-659-related &gt;=Grade 2 nonhematologic toxicities that required dose reduction or discontinuation of therapy.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of Participants Who Discontinued Study Drug Due to TEAEs</measure>
    <time_frame>From first dose of study drug up to 28 days after the last dose of study drug or before the start of subsequent anticancer therapy (up to Cycle 31) (Cycle length =28 days)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Cmax: Maximum Observed Plasma Concentration for TAK-659 on Cycle 1 Day 1</measure>
    <time_frame>Cycle 1 Day 1: pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length= 28 days)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Cmax: Maximum Observed Plasma Concentration for TAK-659 on Cycle 1 Day 7 (Dosing Schedule B) and Cycle 1 Day 15 (Dosing Schedule A)</measure>
    <time_frame>Cycle 1 Day 7 (Dosing Schedule B) and Day 15 (Dosing Schedule A): pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length= 28 days)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-659 on Cycle 1 Day 1</measure>
    <time_frame>Cycle 1 Day 1: pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length= 28 days)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-659 on Cycle 1 Day 7 (Dosing Schedule B) and Cycle 1 Day 15 (Dosing Schedule A)</measure>
    <time_frame>Cycle 1 Day 7 (Dosing Schedule B) and Day 15 (Dosing Schedule A): pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length= 28 days)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>AUCτ: Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for TAK-659 on Cycle 1 Day 1</measure>
    <time_frame>Cycle 1 Day 1: pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length= 28 days)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>AUCτ: Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for TAK-659 on Cycle 1 Day 7 (Dosing Schedule B) and Day 15 (Dosing Schedule A)</measure>
    <time_frame>Cycle 1 Day 7 (Dosing Schedule B) and Day 15 (Dosing Schedule A): pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length= 28 days)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>CLR: Renal Clearance for TAK-659 on Cycle 1 Day 15</measure>
    <time_frame>Cycle 1 Day 15: pre-dose and at multiple time points (up to 8 hours) post-dose (Cycle length= 28 days)</time_frame>
  </primary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">17</enrollment>
  <condition>Lymphoma, Non-Hodgkin</condition>
  <condition>Lymphoma, Follicular, Marginal Zone</condition>
  <arm_group>
    <arm_group_label>Dose Escalation Part Schedule A: TAK-659 60 mg in Cohort 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>TAK-659, tablet, orally, once daily, in a 28-day treatment cycle for up to 12 months or until disease progression or unacceptable toxicity, with a starting dose of 60 milligram (mg) in Cohort 1. Dose escalation will follow a standard 3+3 schema . If 60 mg, once daily is safe and tolerable, then the dose will be escalated to 80 mg, once daily and subsequently in 20 mg increments until MTD and/or RP2D is determined. Based on emerging safety, tolerability, PK data, a lower dose will be permitted.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose Escalation Part Schedule B: TAK-659 80 mg in Cohort 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>TAK-659, tablet, orally, once daily as 7 days on and 7 days off treatment (dosing on 7 days followed by 7 days of rest) in a 28-day treatment cycle for up to 12 months or until disease progression or unacceptable toxicity, with a starting dose of 80 mg in Cohort 1. Dose escalation will follow a standard 3+3 schema. An alternative intermittent regimen may be evaluated if deemed necessary per the emerging data.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Expansion Part: TAK-659 MTD/RP2D</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>TAK-659, tablet, orally, once daily, in a 28-day treatment cycle until disease progression or unacceptable toxicity in participants with follicular lymphoma (FL) or marginal zone lymphoma (MZL) who are relapsed and/or refractory. Dose and dosing schedule for this part will be MTD/RP2D determined from results of dose escalation part.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TAK-659</intervention_name>
    <description>TAK-659 Tablets.</description>
    <arm_group_label>Dose Escalation Part Schedule A: TAK-659 60 mg in Cohort 1</arm_group_label>
    <arm_group_label>Dose Escalation Part Schedule B: TAK-659 80 mg in Cohort 1</arm_group_label>
    <arm_group_label>Expansion Part: TAK-659 MTD/RP2D</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. To be enrolled to the dose escalation part, participants must have histologically or&#xD;
             cytologically confirmed diagnosis of NHL for which no effective standard treatment is&#xD;
             available.&#xD;
&#xD;
          2. To be enrolled in the expansion part, participants must meet the following criteria:&#xD;
&#xD;
               1. Must have pathologically confirmed FL (Grade 1, 2, or 3A) or MZL.&#xD;
&#xD;
               2. Relapsed and/or refractory to &gt;=2 prior lines of chemotherapy based on standard&#xD;
                  of care that include at least 1 anti-CD20-based regimen, as well as alkylating&#xD;
                  agents (example cyclophosphamide or bendamustine).&#xD;
&#xD;
               3. Participants must be ineligible for or refusal to hematopoietic stem cell&#xD;
                  transplant.&#xD;
&#xD;
               4. If the participants have relapsed or progressed after achieving a response&#xD;
                  (defined as CR or PR), documented, investigator-assessed relapse or progression&#xD;
                  after the last treatment is required.&#xD;
&#xD;
          3. Measurable disease per IWG 2007 criteria.&#xD;
&#xD;
          4. Eastern Cooperative Oncology Group performance status score of 0 or 1.&#xD;
&#xD;
          5. Life expectancy of longer than 3 months.&#xD;
&#xD;
          6. Adequate organ function, including the following:&#xD;
&#xD;
               1. Bone marrow reserve: absolute neutrophil count &gt;=1,000 per cubic millimeter&#xD;
                  (/mm^3), platelet count &gt;=75,000/mm^3 (&gt;=50,000/mm^3 for participants with bone&#xD;
                  marrow involvement), and hemoglobin &gt;=8 gram per deciliter (g/dL) (red blood cell&#xD;
                  [RBC] and platelet transfusion allowed &gt;=14 days before assessment).&#xD;
&#xD;
               2. Hepatic function: total bilirubin less than or equal to (&lt;=) 1.5*the upper limit&#xD;
                  of the normal range (ULN); alanine aminotransferase and aspartate&#xD;
                  aminotransferase &lt;=2.5*ULN.&#xD;
&#xD;
               3. Renal function: creatinine clearance &gt;=60 milliliter per minute (mL/min) either&#xD;
                  as estimated by the Cockcroft-Gault equation.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Central nervous system (CNS) lymphoma; active brain or leptomeningeal metastases as&#xD;
             indicated by positive cytology from lumbar puncture or computed tomography&#xD;
             (CT)/magnetic resonance imaging (MRI) by local assessment.&#xD;
&#xD;
          2. Systemic anticancer treatment (including investigational agents) less than 3 weeks&#xD;
             before the first dose of study treatment (&lt;=4 weeks for antibody-based therapy&#xD;
             including unconjugated antibody, antibody-drug conjugate, and bi-specific T-cell&#xD;
             engager agent; &lt;=8 weeks for cell-based therapy or anti-tumor vaccine).&#xD;
&#xD;
          3. Radiotherapy less than (&lt;) 3 weeks before the first dose of study treatment. If prior&#xD;
             radiotherapy occurred &lt;4 to 6 weeks before the study start, as radiated lesions cannot&#xD;
             be reliably assessed by fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography&#xD;
             (PET), nonradiated target lesions are required for eligibility.&#xD;
&#xD;
          4. Prior autologous stem cell transplant (ASCT) within 6 months or prior ASCT at any time&#xD;
             without full hematopoietic recovery before Cycle 1 Day 1, or allogeneic stem cell&#xD;
             transplant at any time.&#xD;
&#xD;
          5. Any clinically significant comorbidities, such as uncontrolled pulmonary disease&#xD;
             (example, severe chronic obstructive pulmonary disease with hypoxemia, interstitial&#xD;
             lung disease, radiation induced lung injury), known impaired cardiac function or&#xD;
             clinically significant cardiac disease, active CNS disease, or any other condition&#xD;
             that could, in the opinion of the investigator, compromise the participant's safety&#xD;
             and participation in the study per protocol.&#xD;
&#xD;
          6. Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral&#xD;
             absorption or tolerance of TAK-659.&#xD;
&#xD;
          7. Use or consumption of any of the following substances:&#xD;
&#xD;
        Received medications, supplements, or food/beverages that are P-glycoprotein (P-gp)&#xD;
        inhibitors or inducers or strong cytochrome P450 (CYP) 3A inhibitors or inducers within a&#xD;
        certain time frame prior to the first dose of study drug. Depending on the substance, the&#xD;
        washout period for P-gp inhibitors or inducers or strong CYP3A inhibitors or inducers will&#xD;
        be either 7 days or 5 times the half-life (half-life is related to the time required for&#xD;
        elimination from the body). The washout period for grapefruit containing food or beverages&#xD;
        is 5 days.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Study Director</last_name>
    <role>Study Director</role>
    <affiliation>Takeda</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>NHO Nagoya Medical Center</name>
      <address>
        <city>Nagoya-shi</city>
        <state>Aichi</state>
        <zip>460-0001</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Cancer Center Hospital</name>
      <address>
        <city>Chuo-ku</city>
        <state>Tokyo</state>
        <zip>104-0045</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seoul National University Hospital</name>
      <address>
        <city>Seoul</city>
        <zip>3080</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Samsung Medical Center</name>
      <address>
        <city>Seoul</city>
        <zip>6315</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Japan</country>
    <country>Korea, Republic of</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>August 1, 2017</study_first_submitted>
  <study_first_submitted_qc>August 1, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 3, 2017</study_first_posted>
  <results_first_submitted>August 17, 2021</results_first_submitted>
  <results_first_submitted_qc>August 17, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">September 14, 2021</results_first_posted>
  <last_update_submitted>February 6, 2023</last_update_submitted>
  <last_update_submitted_qc>February 6, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 8, 2023</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>Lymphoma</mesh_term>
    <mesh_term>Lymphoma, Non-Hodgkin</mesh_term>
    <mesh_term>Lymphoma, Follicular</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_access_criteria>IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.</ipd_access_criteria>
    <ipd_url>https://vivli.org/ourmember/takeda/</ipd_url>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>December 6, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/51/NCT03238651/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>February 20, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/51/NCT03238651/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants took part in the study at 5 investigative sites in Japan and South Korea from 1 August 2017 to 17 August 2020.</recruitment_details>
      <pre_assignment_details>Participants with non-Hodgkin lymphoma (NHL) were enrolled in 1 of the 2 treatment schedules in the Dose Escalation Part to receive TAK-659: Dosing Schedule A and Dosing Schedule B. Dose Expansion part was not initiated and the data for secondary outcome measures was not analyzed due to early termination of the study by the sponsor due to business decision.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Dose Escalation Part, Dosing Schedule A: TAK-659 40 mg</title>
          <description>TAK-659 40 milligram (mg), tablet, orally, once daily, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
        </group>
        <group group_id="P2">
          <title>Dose Escalation Part, Dosing Schedule A: TAK-659 60 mg</title>
          <description>TAK-659 60 mg, tablet, orally, once daily, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
        </group>
        <group group_id="P3">
          <title>Dose Escalation Part, Dosing Schedule A: TAK-659 80 mg</title>
          <description>TAK-659 80 mg, tablet, orally, once daily, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
        </group>
        <group group_id="P4">
          <title>Dose Escalation Part, Dosing Schedule B: TAK-659 80 mg</title>
          <description>TAK-659 80 mg, tablet, orally, once daily as 7 days on and 7 days off treatment (dosing on 7 days followed by 7 days of rest) in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
        </group>
        <group group_id="P5">
          <title>Dose Escalation Part, Dosing Schedule B: TAK-659 100 mg</title>
          <description>TAK-659 100 mg, tablet, orally, once daily as 7 days on and 7 days off treatment (dosing on 7 days followed by 7 days of rest) in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="4"/>
                <participants group_id="P4" count="3"/>
                <participants group_id="P5" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="4"/>
                <participants group_id="P4" count="3"/>
                <participants group_id="P5" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Other</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Progressive Disease</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="2"/>
                <participants group_id="P4" count="2"/>
                <participants group_id="P5" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="1"/>
                <participants group_id="P5" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="2"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The safety analysis set included participants who received at least 1 dose of study drug.</population>
      <group_list>
        <group group_id="B1">
          <title>Dose Escalation Part, Dosing Schedule A: TAK-659 40 mg</title>
          <description>TAK-659 40 mg, tablet, orally, once daily, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
        </group>
        <group group_id="B2">
          <title>Dose Escalation Part, Dosing Schedule A: TAK-659 60 mg</title>
          <description>TAK-659 60 mg, tablet, orally, once daily, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
        </group>
        <group group_id="B3">
          <title>Dose Escalation Part, Dosing Schedule A: TAK-659 80 mg</title>
          <description>TAK-659 80 mg, tablet, orally, once daily, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
        </group>
        <group group_id="B4">
          <title>Dose Escalation Part, Dosing Schedule B: TAK-659 80 mg</title>
          <description>TAK-659 80 mg, tablet, orally, once daily as 7 days on and 7 days off treatment (dosing on 7 days followed by 7 days of rest) in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
        </group>
        <group group_id="B5">
          <title>Dose Escalation Part, Dosing Schedule B: TAK-659 100 mg</title>
          <description>TAK-659 100 mg, tablet, orally, once daily as 7 days on and 7 days off treatment (dosing on 7 days followed by 7 days of rest) in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
        </group>
        <group group_id="B6">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="3"/>
            <count group_id="B2" value="6"/>
            <count group_id="B3" value="4"/>
            <count group_id="B4" value="3"/>
            <count group_id="B5" value="1"/>
            <count group_id="B6" value="17"/>
          </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="66.7" spread="8.50"/>
                    <measurement group_id="B2" value="64.5" spread="19.46"/>
                    <measurement group_id="B3" value="63.3" spread="8.92"/>
                    <measurement group_id="B4" value="65.7" spread="2.89"/>
                    <measurement group_id="B5" value="67.0"/>
                    <measurement group_id="B6" value="64.9" spread="12.04"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="1"/>
                    <measurement group_id="B6" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="12"/>
                  </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 group_id="B6" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="3"/>
                    <measurement group_id="B5" value="1"/>
                    <measurement group_id="B6" value="17"/>
                  </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 group_id="B6" 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 group_id="B6" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="3"/>
                    <measurement group_id="B5" value="1"/>
                    <measurement group_id="B6" value="17"/>
                  </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 group_id="B6" 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 group_id="B6" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</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 group_id="B6" value="0"/>
                  </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 group_id="B6" 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 group_id="B6" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Japan</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Korea, Republic Of</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="1"/>
                    <measurement group_id="B6" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)</title>
        <time_frame>From first dose of study drug up to 28 days after the last dose of study drug or before the start of subsequent anticancer therapy (up to Cycle 31) (Cycle length =28 days)</time_frame>
        <population>The safety analysis set included participants who received at least 1 dose of study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>Dose Escalation Part, Schedule Dosing A: TAK-659 40 mg</title>
            <description>TAK-659 40 mg, tablet, orally, once daily, in a 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
          </group>
          <group group_id="O2">
            <title>Dose Escalation Part, Dosing Schedule A: TAK-659 60 mg</title>
            <description>TAK-659 60 mg, tablet, orally, once daily, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
          </group>
          <group group_id="O3">
            <title>Dose Escalation Part, Dosing Schedule A: TAK-659 80 mg</title>
            <description>TAK-659 80 mg, tablet, orally, once daily, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
          </group>
          <group group_id="O4">
            <title>Dose Escalation Part, Dosing Schedule B: TAK-659 80 mg</title>
            <description>TAK-659 80 mg, tablet, orally, once daily as 7 days on and 7 days off treatment (dosing on 7 days followed by 7 days of rest) in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
          </group>
          <group group_id="O5">
            <title>Dose Escalation Part, Dosing Schedule B: TAK-659 100 mg</title>
            <description>TAK-659 100 mg, tablet, orally, once daily as 7 days on and 7 days off treatment (dosing on 7 days followed by 7 days of rest) in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)</title>
          <population>The safety analysis set included participants who received at least 1 dose of study drug.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="4"/>
                <count group_id="O4" value="3"/>
                <count group_id="O5" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100"/>
                    <measurement group_id="O2" value="100"/>
                    <measurement group_id="O3" value="100"/>
                    <measurement group_id="O4" value="100"/>
                    <measurement group_id="O5" value="100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Participants With Grade 3 or Higher TEAEs</title>
        <description>TEAEs were graded as per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03. As per the NCI-CTCAE, Grade 1 (mild, asymptomatic or mild symptoms); Grade 2 (moderate, minimal, local or noninvasive intervention indicated); Grade 3 (severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated); Grade 4 (life-threatening consequences, urgent intervention indicated); Grade 5 (death related to adverse event [AE]).</description>
        <time_frame>From first dose of study drug up to 28 days after the last dose of study drug or before the start of subsequent anticancer therapy (up to Cycle 31) (Cycle length =28 days)</time_frame>
        <population>The safety analysis set included participants who received at least 1 dose of study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>Dose Escalation Part, Schedule Dosing A: TAK-659 40 mg</title>
            <description>TAK-659 40 mg, tablet, orally, once daily, in a 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
          </group>
          <group group_id="O2">
            <title>Dose Escalation Part, Dosing Schedule A: TAK-659 60 mg</title>
            <description>TAK-659 60 mg, tablet, orally, once daily, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
          </group>
          <group group_id="O3">
            <title>Dose Escalation Part, Dosing Schedule A: TAK-659 80 mg</title>
            <description>TAK-659 80 mg, tablet, orally, once daily, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
          </group>
          <group group_id="O4">
            <title>Dose Escalation Part, Dosing Schedule B: TAK-659 80 mg</title>
            <description>TAK-659 80 mg, tablet, orally, once daily as 7 days on and 7 days off treatment (dosing on 7 days followed by 7 days of rest) in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
          </group>
          <group group_id="O5">
            <title>Dose Escalation Part, Dosing Schedule B: TAK-659 100 mg</title>
            <description>TAK-659 100 mg, tablet, orally, once daily as 7 days on and 7 days off treatment (dosing on 7 days followed by 7 days of rest) in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Grade 3 or Higher TEAEs</title>
          <description>TEAEs were graded as per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03. As per the NCI-CTCAE, Grade 1 (mild, asymptomatic or mild symptoms); Grade 2 (moderate, minimal, local or noninvasive intervention indicated); Grade 3 (severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated); Grade 4 (life-threatening consequences, urgent intervention indicated); Grade 5 (death related to adverse event [AE]).</description>
          <population>The safety analysis set included participants who received at least 1 dose of study drug.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="4"/>
                <count group_id="O4" value="3"/>
                <count group_id="O5" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="66.7"/>
                    <measurement group_id="O2" value="100"/>
                    <measurement group_id="O3" value="100"/>
                    <measurement group_id="O4" value="100"/>
                    <measurement group_id="O5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Participants With Serious TEAEs</title>
        <time_frame>From first dose of study drug up to 28 days after the last dose of study drug or before the start of subsequent anticancer therapy (up to Cycle 31) (Cycle length =28 days)</time_frame>
        <population>The safety analysis set included participants who received at least 1 dose of study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>Dose Escalation Part, Schedule Dosing A: TAK-659 40 mg</title>
            <description>TAK-659 40 mg, tablet, orally, once daily, in a 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
          </group>
          <group group_id="O2">
            <title>Dose Escalation Part, Dosing Schedule A: TAK-659 60 mg</title>
            <description>TAK-659 60 mg, tablet, orally, once daily, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
          </group>
          <group group_id="O3">
            <title>Dose Escalation Part, Dosing Schedule A: TAK-659 80 mg</title>
            <description>TAK-659 80 mg, tablet, orally, once daily, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
          </group>
          <group group_id="O4">
            <title>Dose Escalation Part, Dosing Schedule B: TAK-659 80 mg</title>
            <description>TAK-659 80 mg, tablet, orally, once daily as 7 days on and 7 days off treatment (dosing on 7 days followed by 7 days of rest) in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
          </group>
          <group group_id="O5">
            <title>Dose Escalation Part, Dosing Schedule B: TAK-659 100 mg</title>
            <description>TAK-659 100 mg, tablet, orally, once daily as 7 days on and 7 days off treatment (dosing on 7 days followed by 7 days of rest) in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Serious TEAEs</title>
          <population>The safety analysis set included participants who received at least 1 dose of study drug.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="4"/>
                <count group_id="O4" value="3"/>
                <count group_id="O5" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="100"/>
                    <measurement group_id="O3" value="75"/>
                    <measurement group_id="O4" value="33.3"/>
                    <measurement group_id="O5" value="100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Dose Escalation Part: Percentage of Participants With Dose-limiting Toxicities (DLTs) During Cycle 1</title>
        <description>DLT was evaluated as per NCI-CTCAE, v4.03 and defined as any of the following events occurring during Cycle 1 that were considered by the investigator to be possibly related to therapy: Grade 4 neutropenia unresolved to less than or equal to (&lt;=) Grade 1 or baseline for more than 7 days in the absence of growth factor support; greater than or equal to (&gt;=) Grade 3 neutropenia with fever and/or infection;Grade 4 thrombocytopenia unresolved to &lt;=Grade 1 or baseline for more than 7 days; &gt;=Grade 3 thrombocytopenia with clinically significant bleeding; Grade &gt;=3 nonhematologic toxicity except for treated &gt;=Grade 3 nausea and/or emesis and diarrhea resolved to less than (&lt;) Grade 3 within 3 days, Grade 3 fatigue &lt;=72 hours, isolated asymptomatic &gt;=Grade 3 laboratory abnormalities resolved to &lt;=Grade 1 or baseline in &lt;=7 days;received &lt;75% of planned doses of study drug in Cycle 1;TAK-659-related &gt;=Grade 2 nonhematologic toxicities that required dose reduction or discontinuation of therapy.</description>
        <time_frame>Cycle 1 (Cycle length =28 days)</time_frame>
        <population>DLT-evaluable analysis set included participants who met the minimum treatment and safety evaluation requirements of the study or who experienced a DLT during Cycle 1. As planned, this outcome measure was analyzed and reported for dose escalation part only.</population>
        <group_list>
          <group group_id="O1">
            <title>Dose Escalation Part, Schedule Dosing A: TAK-659 40 mg</title>
            <description>TAK-659 40 mg, tablet, orally, once daily, in a 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
          </group>
          <group group_id="O2">
            <title>Dose Escalation Part, Dosing Schedule A: TAK-659 60 mg</title>
            <description>TAK-659 60 mg, tablet, orally, once daily, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
          </group>
          <group group_id="O3">
            <title>Dose Escalation Part, Dosing Schedule A: TAK-659 80 mg</title>
            <description>TAK-659 80 mg, tablet, orally, once daily, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
          </group>
          <group group_id="O4">
            <title>Dose Escalation Part, Dosing Schedule B: TAK-659 80 mg</title>
            <description>TAK-659 80 mg, tablet, orally, once daily as 7 days on and 7 days off treatment (dosing on 7 days followed by 7 days of rest) in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
          </group>
          <group group_id="O5">
            <title>Dose Escalation Part, Dosing Schedule B: TAK-659 100 mg</title>
            <description>TAK-659 100 mg, tablet, orally, once daily as 7 days on and 7 days off treatment (dosing on 7 days followed by 7 days of rest) in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
          </group>
        </group_list>
        <measure>
          <title>Dose Escalation Part: Percentage of Participants With Dose-limiting Toxicities (DLTs) During Cycle 1</title>
          <description>DLT was evaluated as per NCI-CTCAE, v4.03 and defined as any of the following events occurring during Cycle 1 that were considered by the investigator to be possibly related to therapy: Grade 4 neutropenia unresolved to less than or equal to (&lt;=) Grade 1 or baseline for more than 7 days in the absence of growth factor support; greater than or equal to (&gt;=) Grade 3 neutropenia with fever and/or infection;Grade 4 thrombocytopenia unresolved to &lt;=Grade 1 or baseline for more than 7 days; &gt;=Grade 3 thrombocytopenia with clinically significant bleeding; Grade &gt;=3 nonhematologic toxicity except for treated &gt;=Grade 3 nausea and/or emesis and diarrhea resolved to less than (&lt;) Grade 3 within 3 days, Grade 3 fatigue &lt;=72 hours, isolated asymptomatic &gt;=Grade 3 laboratory abnormalities resolved to &lt;=Grade 1 or baseline in &lt;=7 days;received &lt;75% of planned doses of study drug in Cycle 1;TAK-659-related &gt;=Grade 2 nonhematologic toxicities that required dose reduction or discontinuation of therapy.</description>
          <population>DLT-evaluable analysis set included participants who met the minimum treatment and safety evaluation requirements of the study or who experienced a DLT during Cycle 1. As planned, this outcome measure was analyzed and reported for dose escalation part only.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="4"/>
                <count group_id="O4" value="3"/>
                <count group_id="O5" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="16.7"/>
                    <measurement group_id="O3" value="50"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Participants Who Discontinued Study Drug Due to TEAEs</title>
        <time_frame>From first dose of study drug up to 28 days after the last dose of study drug or before the start of subsequent anticancer therapy (up to Cycle 31) (Cycle length =28 days)</time_frame>
        <population>The safety analysis set included participants who received at least 1 dose of study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>Dose Escalation Part, Schedule Dosing A: TAK-659 40 mg</title>
            <description>TAK-659 40 mg, tablet, orally, once daily, in a 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
          </group>
          <group group_id="O2">
            <title>Dose Escalation Part, Dosing Schedule A: TAK-659 60 mg</title>
            <description>TAK-659 60 mg, tablet, orally, once daily, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
          </group>
          <group group_id="O3">
            <title>Dose Escalation Part, Dosing Schedule A: TAK-659 80 mg</title>
            <description>TAK-659 80 mg, tablet, orally, once daily, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
          </group>
          <group group_id="O4">
            <title>Dose Escalation Part, Dosing Schedule B: TAK-659 80 mg</title>
            <description>TAK-659 80 mg, tablet, orally, once daily as 7 days on and 7 days off treatment (dosing on 7 days followed by 7 days of rest) in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
          </group>
          <group group_id="O5">
            <title>Dose Escalation Part, Dosing Schedule B: TAK-659 100 mg</title>
            <description>TAK-659 100 mg, tablet, orally, once daily as 7 days on and 7 days off treatment (dosing on 7 days followed by 7 days of rest) in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Who Discontinued Study Drug Due to TEAEs</title>
          <population>The safety analysis set included participants who received at least 1 dose of study drug.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="4"/>
                <count group_id="O4" value="3"/>
                <count group_id="O5" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33.3"/>
                    <measurement group_id="O2" value="50"/>
                    <measurement group_id="O3" value="50"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Cmax: Maximum Observed Plasma Concentration for TAK-659 on Cycle 1 Day 1</title>
        <time_frame>Cycle 1 Day 1: pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length= 28 days)</time_frame>
        <population>The pharmacokinetic (PK) analysis set included participants who had sufficient dosing and PK data to reliably estimate 1 or more PK parameters.</population>
        <group_list>
          <group group_id="O1">
            <title>Dose Escalation Part, Schedule Dosing A: TAK-659 40 mg</title>
            <description>TAK-659 40 mg, tablet, orally, once daily, in a 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
          </group>
          <group group_id="O2">
            <title>Dose Escalation Part, Dosing Schedule A: TAK-659 60 mg</title>
            <description>TAK-659 60 mg, tablet, orally, once daily, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
          </group>
          <group group_id="O3">
            <title>Dose Escalation Part, Dosing Schedule A: TAK-659 80 mg</title>
            <description>TAK-659 80 mg, tablet, orally, once daily, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
          </group>
          <group group_id="O4">
            <title>Dose Escalation Part, Dosing Schedule B: TAK-659 80 mg</title>
            <description>TAK-659 80 mg, tablet, orally, once daily as 7 days on and 7 days off treatment (dosing on 7 days followed by 7 days of rest) in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
          </group>
          <group group_id="O5">
            <title>Dose Escalation Part, Dosing Schedule B: TAK-659 100 mg</title>
            <description>TAK-659 100 mg, tablet, orally, once daily as 7 days on and 7 days off treatment (dosing on 7 days followed by 7 days of rest) in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
          </group>
        </group_list>
        <measure>
          <title>Cmax: Maximum Observed Plasma Concentration for TAK-659 on Cycle 1 Day 1</title>
          <population>The pharmacokinetic (PK) analysis set included participants who had sufficient dosing and PK data to reliably estimate 1 or more PK parameters.</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="3"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="4"/>
                <count group_id="O4" value="3"/>
                <count group_id="O5" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="93.86" spread="62.88"/>
                    <measurement group_id="O2" value="127.65" spread="22.39"/>
                    <measurement group_id="O3" value="214.50" spread="74.67"/>
                    <measurement group_id="O4" value="216.00" spread="18.01"/>
                    <measurement group_id="O5" value="297.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Cmax: Maximum Observed Plasma Concentration for TAK-659 on Cycle 1 Day 7 (Dosing Schedule B) and Cycle 1 Day 15 (Dosing Schedule A)</title>
        <time_frame>Cycle 1 Day 7 (Dosing Schedule B) and Day 15 (Dosing Schedule A): pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length= 28 days)</time_frame>
        <population>The PK analysis set included participants who had sufficient dosing and PK data to reliably estimate 1 or more PK parameters. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Dose Escalation Part, Schedule Dosing A: TAK-659 40 mg</title>
            <description>TAK-659 40 mg, tablet, orally, once daily, in a 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
          </group>
          <group group_id="O2">
            <title>Dose Escalation Part, Dosing Schedule A: TAK-659 60 mg</title>
            <description>TAK-659 60 mg, tablet, orally, once daily, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
          </group>
          <group group_id="O3">
            <title>Dose Escalation Part, Dosing Schedule A: TAK-659 80 mg</title>
            <description>TAK-659 80 mg, tablet, orally, once daily, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
          </group>
          <group group_id="O4">
            <title>Dose Escalation Part, Dosing Schedule B: TAK-659 80 mg</title>
            <description>TAK-659 80 mg, tablet, orally, once daily as 7 days on and 7 days off treatment (dosing on 7 days followed by 7 days of rest) in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
          </group>
          <group group_id="O5">
            <title>Dose Escalation Part, Dosing Schedule B: TAK-659 100 mg</title>
            <description>TAK-659 100 mg, tablet, orally, once daily as 7 days on and 7 days off treatment (dosing on 7 days followed by 7 days of rest) in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
          </group>
        </group_list>
        <measure>
          <title>Cmax: Maximum Observed Plasma Concentration for TAK-659 on Cycle 1 Day 7 (Dosing Schedule B) and Cycle 1 Day 15 (Dosing Schedule A)</title>
          <population>The PK analysis set included participants who had sufficient dosing and PK data to reliably estimate 1 or more PK parameters. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure.</population>
          <units>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="3"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="2"/>
                <count group_id="O4" value="3"/>
                <count group_id="O5" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="121.18" spread="39.57"/>
                    <measurement group_id="O2" value="130.23" spread="62.95"/>
                    <measurement group_id="O3" value="308.29" spread="53.67"/>
                    <measurement group_id="O4" value="339.42" spread="29.96"/>
                    <measurement group_id="O5" value="329.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-659 on Cycle 1 Day 1</title>
        <time_frame>Cycle 1 Day 1: pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length= 28 days)</time_frame>
        <population>The PK analysis set included participants who had sufficient dosing and PK data to reliably estimate 1 or more PK parameters.</population>
        <group_list>
          <group group_id="O1">
            <title>Dose Escalation Part, Schedule Dosing A: TAK-659 40 mg</title>
            <description>TAK-659 40 mg, tablet, orally, once daily, in a 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
          </group>
          <group group_id="O2">
            <title>Dose Escalation Part, Dosing Schedule A: TAK-659 60 mg</title>
            <description>TAK-659 60 mg, tablet, orally, once daily, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
          </group>
          <group group_id="O3">
            <title>Dose Escalation Part, Dosing Schedule A: TAK-659 80 mg</title>
            <description>TAK-659 80 mg, tablet, orally, once daily, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
          </group>
          <group group_id="O4">
            <title>Dose Escalation Part, Dosing Schedule B: TAK-659 80 mg</title>
            <description>TAK-659 80 mg, tablet, orally, once daily as 7 days on and 7 days off treatment (dosing on 7 days followed by 7 days of rest) in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
          </group>
          <group group_id="O5">
            <title>Dose Escalation Part, Dosing Schedule B: TAK-659 100 mg</title>
            <description>TAK-659 100 mg, tablet, orally, once daily as 7 days on and 7 days off treatment (dosing on 7 days followed by 7 days of rest) in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
          </group>
        </group_list>
        <measure>
          <title>Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-659 on Cycle 1 Day 1</title>
          <population>The PK analysis set included participants who had sufficient dosing and PK data to reliably estimate 1 or more PK parameters.</population>
          <units>hours</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="4"/>
                <count group_id="O4" value="3"/>
                <count group_id="O5" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.97" lower_limit="1.0" upper_limit="3.0"/>
                    <measurement group_id="O2" value="3.01" lower_limit="1.9" upper_limit="4.0"/>
                    <measurement group_id="O3" value="2.00" lower_limit="0.5" upper_limit="3.0"/>
                    <measurement group_id="O4" value="2.05" lower_limit="0.5" upper_limit="2.7"/>
                    <measurement group_id="O5" value="2.00" lower_limit="2.0" upper_limit="2.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-659 on Cycle 1 Day 7 (Dosing Schedule B) and Cycle 1 Day 15 (Dosing Schedule A)</title>
        <time_frame>Cycle 1 Day 7 (Dosing Schedule B) and Day 15 (Dosing Schedule A): pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length= 28 days)</time_frame>
        <population>The PK analysis set included participants who had sufficient dosing and PK data to reliably estimate 1 or more PK parameters. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Dose Escalation Part, Schedule Dosing A: TAK-659 40 mg</title>
            <description>TAK-659 40 mg, tablet, orally, once daily, in a 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
          </group>
          <group group_id="O2">
            <title>Dose Escalation Part, Dosing Schedule A: TAK-659 60 mg</title>
            <description>TAK-659 60 mg, tablet, orally, once daily, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
          </group>
          <group group_id="O3">
            <title>Dose Escalation Part, Dosing Schedule A: TAK-659 80 mg</title>
            <description>TAK-659 80 mg, tablet, orally, once daily, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
          </group>
          <group group_id="O4">
            <title>Dose Escalation Part, Dosing Schedule B: TAK-659 80 mg</title>
            <description>TAK-659 80 mg, tablet, orally, once daily as 7 days on and 7 days off treatment (dosing on 7 days followed by 7 days of rest) in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
          </group>
          <group group_id="O5">
            <title>Dose Escalation Part, Dosing Schedule B: TAK-659 100 mg</title>
            <description>TAK-659 100 mg, tablet, orally, once daily as 7 days on and 7 days off treatment (dosing on 7 days followed by 7 days of rest) in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
          </group>
        </group_list>
        <measure>
          <title>Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-659 on Cycle 1 Day 7 (Dosing Schedule B) and Cycle 1 Day 15 (Dosing Schedule A)</title>
          <population>The PK analysis set included participants who had sufficient dosing and PK data to reliably estimate 1 or more PK parameters. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure.</population>
          <units>hours</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="2"/>
                <count group_id="O4" value="3"/>
                <count group_id="O5" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.00" lower_limit="0.5" upper_limit="3.1"/>
                    <measurement group_id="O2" value="3.01" lower_limit="0.0" upper_limit="4.1"/>
                    <measurement group_id="O3" value="2.25" lower_limit="0.5" upper_limit="4.0"/>
                    <measurement group_id="O4" value="2.00" lower_limit="0.9" upper_limit="2.0"/>
                    <measurement group_id="O5" value="1.00" lower_limit="1.0" upper_limit="1.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>AUCτ: Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for TAK-659 on Cycle 1 Day 1</title>
        <time_frame>Cycle 1 Day 1: pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length= 28 days)</time_frame>
        <population>The PK analysis set included participants who had sufficient dosing and PK data to reliably estimate 1 or more PK parameters.</population>
        <group_list>
          <group group_id="O1">
            <title>Dose Escalation Part, Schedule Dosing A: TAK-659 40 mg</title>
            <description>TAK-659 40 mg, tablet, orally, once daily, in a 28-days treatment cycle disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
          </group>
          <group group_id="O2">
            <title>Dose Escalation Part, Dosing Schedule A: TAK-659 60 mg</title>
            <description>TAK-659 60 mg, tablet, orally, once daily, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
          </group>
          <group group_id="O3">
            <title>Dose Escalation Part, Dosing Schedule A: TAK-659 80 mg</title>
            <description>TAK-659 80 mg, tablet, orally, once daily, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
          </group>
          <group group_id="O4">
            <title>Dose Escalation Part, Dosing Schedule B: TAK-659 80 mg</title>
            <description>TAK-659 80 mg, tablet, orally, once daily as 7 days on and 7 days off treatment (dosing on 7 days followed by 7 days of rest) in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
          </group>
          <group group_id="O5">
            <title>Dose Escalation Part, Dosing Schedule B: TAK-659 100 mg</title>
            <description>TAK-659 100 mg, tablet, orally, once daily as 7 days on and 7 days off treatment (dosing on 7 days followed by 7 days of rest) in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
          </group>
        </group_list>
        <measure>
          <title>AUCτ: Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for TAK-659 on Cycle 1 Day 1</title>
          <population>The PK analysis set included participants who had sufficient dosing and PK data to reliably estimate 1 or more PK parameters.</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="3"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="4"/>
                <count group_id="O4" value="3"/>
                <count group_id="O5" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="587.2534" spread="22.2886"/>
                    <measurement group_id="O2" value="1207.6554" spread="26.3167"/>
                    <measurement group_id="O3" value="1742.7394" spread="39.3327"/>
                    <measurement group_id="O4" value="1899.2508" spread="15.1827"/>
                    <measurement group_id="O5" value="1828.4544"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>AUCτ: Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for TAK-659 on Cycle 1 Day 7 (Dosing Schedule B) and Day 15 (Dosing Schedule A)</title>
        <time_frame>Cycle 1 Day 7 (Dosing Schedule B) and Day 15 (Dosing Schedule A): pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length= 28 days)</time_frame>
        <population>The PK analysis set included participants who had sufficient dosing and PK data to reliably estimate 1 or more PK parameters. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Dose Escalation Part, Schedule Dosing A: TAK-659 40 mg</title>
            <description>TAK-659 40 mg, tablet, orally, once daily, in a 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
          </group>
          <group group_id="O2">
            <title>Dose Escalation Part, Dosing Schedule A: TAK-659 60 mg</title>
            <description>TAK-659 60 mg, tablet, orally, once daily, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
          </group>
          <group group_id="O3">
            <title>Dose Escalation Part, Dosing Schedule A: TAK-659 80 mg</title>
            <description>TAK-659 80 mg, tablet, orally, once daily, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
          </group>
          <group group_id="O4">
            <title>Dose Escalation Part, Dosing Schedule B: TAK-659 80 mg</title>
            <description>TAK-659 80 mg, tablet, orally, once daily as 7 days on and 7 days off treatment (dosing on 7 days followed by 7 days of rest) in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
          </group>
          <group group_id="O5">
            <title>Dose Escalation Part, Dosing Schedule B: TAK-659 100 mg</title>
            <description>TAK-659 100 mg, tablet, orally, once daily as 7 days on and 7 days off treatment (dosing on 7 days followed by 7 days of rest) in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
          </group>
        </group_list>
        <measure>
          <title>AUCτ: Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for TAK-659 on Cycle 1 Day 7 (Dosing Schedule B) and Day 15 (Dosing Schedule A)</title>
          <population>The PK analysis set included participants who had sufficient dosing and PK data to reliably estimate 1 or more PK parameters. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure.</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="3"/>
                <count group_id="O2" value="5"/>
                <count group_id="O3" value="2"/>
                <count group_id="O4" value="3"/>
                <count group_id="O5" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1114.2391" spread="1.1927"/>
                    <measurement group_id="O2" value="2016.8000" spread="21.3348"/>
                    <measurement group_id="O3" value="3502.3513" spread="25.0980"/>
                    <measurement group_id="O4" value="3349.4133" spread="12.2891"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>CLR: Renal Clearance for TAK-659 on Cycle 1 Day 15</title>
        <time_frame>Cycle 1 Day 15: pre-dose and at multiple time points (up to 8 hours) post-dose (Cycle length= 28 days)</time_frame>
        <population>The PK analysis set included participants who had sufficient dosing and PK data to reliably estimate 1 or more PK parameters. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure. CLR data was planned to be collected and analyzed for both of the Dosing Schedule A and B arms. However, urine sample was not collected in Dosing Schedule B due to administrative reasons. Therefore, data was not analyzed and reported for schedule B arm.</population>
        <group_list>
          <group group_id="O1">
            <title>Dose Escalation Part, Schedule Dosing A: TAK-659 40 mg</title>
            <description>TAK-659 40 mg, tablet, orally, once daily, in a 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
          </group>
          <group group_id="O2">
            <title>Dose Escalation Part, Dosing Schedule A: TAK-659 60 mg</title>
            <description>TAK-659 60 mg, tablet, orally, once daily, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
          </group>
          <group group_id="O3">
            <title>Dose Escalation Part, Dosing Schedule A: TAK-659 80 mg</title>
            <description>TAK-659 80 mg, tablet, orally, once daily, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
          </group>
          <group group_id="O4">
            <title>Dose Escalation Part, Dosing Schedule B: TAK-659 80 mg</title>
            <description>TAK-659 80 mg, tablet, orally, once daily as 7 days on and 7 days off treatment (dosing on 7 days followed by 7 days of rest) in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
          </group>
          <group group_id="O5">
            <title>Dose Escalation Part, Dosing Schedule B: TAK-659 100 mg</title>
            <description>TAK-659 100 mg, tablet, orally, once daily as 7 days on and 7 days off treatment (dosing on 7 days followed by 7 days of rest) in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
          </group>
        </group_list>
        <measure>
          <title>CLR: Renal Clearance for TAK-659 on Cycle 1 Day 15</title>
          <population>The PK analysis set included participants who had sufficient dosing and PK data to reliably estimate 1 or more PK parameters. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure. CLR data was planned to be collected and analyzed for both of the Dosing Schedule A and B arms. However, urine sample was not collected in Dosing Schedule B due to administrative reasons. Therefore, data was not analyzed and reported for schedule B arm.</population>
          <units>liter per hour (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="3"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="2"/>
                <count group_id="O4" value="0"/>
                <count group_id="O5" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.7303" spread="49.0441"/>
                    <measurement group_id="O2" value="8.4185" spread="114.6567"/>
                    <measurement group_id="O3" value="9.4059" spread="22.3501"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Treatment-emergent adverse events were adverse events that started from first dose of study drug up to 28 days after the last dose of study drug or before the start of subsequent anticancer therapy (up to Cycle 31) (Cycle length =28 days)</time_frame>
      <desc>At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.</desc>
      <group_list>
        <group group_id="E1">
          <title>Dose Escalation Part, Dosing Schedule A: TAK-659 40 mg</title>
          <description>TAK-659 40 mg, tablet, orally, once daily, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
        </group>
        <group group_id="E2">
          <title>Dose Escalation Part, Dosing Schedule A: TAK-659 60 mg</title>
          <description>TAK-659 60 mg, tablet, orally, once daily, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
        </group>
        <group group_id="E3">
          <title>Dose Escalation Part, Dosing Schedule A: TAK-659 80 mg</title>
          <description>TAK-659 80 mg, tablet, orally, once daily, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
        </group>
        <group group_id="E4">
          <title>Dose Escalation Part, Dosing Schedule B: TAK-659 80 mg</title>
          <description>TAK-659 80 mg, tablet, orally, once daily as 7 days on and 7 days off treatment (dosing on 7 days followed by 7 days of rest) in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
        </group>
        <group group_id="E5">
          <title>Dose Escalation Part, Dosing Schedule B: TAK-659 100 mg</title>
          <description>TAK-659 100 mg, tablet, orally, once daily as 7 days on and 7 days off treatment (dosing on 7 days followed by 7 days of rest) in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 23.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Febrile neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Pericardial effusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Ventricular extrasystoles</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Jejunal perforation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Diverticulitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Herpes zoster</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Large intestine infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Meningitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Pneumocystis jirovecii pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Pancreatic carcinoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Hydronephrosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA 23.0</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="3" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Ventricular extrasystoles</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Conjunctival haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Dry eye</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Eyelid ptosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Periorbital oedema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Stomatitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Abdominal discomfort</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Haemorrhoids</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Face oedema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Generalised oedema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Hepatic function abnormal</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Cystitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Diverticulitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Herpes zoster</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Otitis media</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Skin infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Arthropod bite</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Amylase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Blood creatine phosphokinase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Lipase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>White blood cell count decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>CD4 lymphocytes decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Blood alkaline phosphatase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Blood creatinine increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Blood lactate dehydrogenase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hypophosphataemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Hypophagia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Hypercalcaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Hyperglycaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Hyperphosphataemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Hyperuricaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Hypoalbuminaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Hypocalcaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Hypomagnesaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Groin pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Musculoskeletal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Neck pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Spinal osteoarthritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Skin papilloma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Hemiparesis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Delirium</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Hallucination</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Dysuria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Pneumonitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Productive cough</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Seborrhoeic dermatitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Dermatitis acneiform</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Drug eruption</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Night sweats</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Pain of skin</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Rash erythematous</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </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>Study 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/NCT03238651
org study id: C34007
secondary id: U1111-1186-6838
nct id: NCT03238651
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to determine the safety, tolerability, maximum tolerated dose
      (MTD) and/or recommended phase 2 dose (RP2D) of TAK-659 when administered in East Asian
      participants with NHL who do not have an effective standard treatment available and to
      characterize the plasma and urine pharmacokinetic (PK) of TAK-659 in East Asian participants
      with NHL.
The drug being tested in this study is called TAK-659. TAK-659 is being tested to treat
      people who have NHL or people who have relapsed and/or refractory NHL. This study will assess
      the safety, tolerability, PK, and preliminary efficacy of single-agent TAK-659 in East Asian
      participants with NHL.

      The study will enroll approximately 33 to 47 participants, including at least 6 Japanese at
      RP2D dose level. Participants will be assigned to one of the following treatment groups:

      Dose Escalation Part: TAK-659 Expansion Part: TAK-659 RP2D

      This multi-center trial will be conducted in Japan and Republic of Korea. The maximum
      duration of participation in dose escalation part of the study is up to 12 months, unless in
      the opinion of the investigator and sponsor the participant would derive benefit from
      continued therapy beyond 12 months. In expansion part, participants who stop treatment for
      any other reason other than PD will continue to have PFS follow-up at the site every 2 months
      from the last dose of study drug up to 6 months or until PD. Participants will be followed 28
      days after last dose of study drug or until the start of subsequent antineoplastic therapy,
      whichever occurs first, for a follow up assessment.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: None (Open Label)
measure: Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)
time frame: From first dose of study drug up to 28 days after the last dose of study drug or before the start of subsequent anticancer therapy (up to Cycle 31) (Cycle length =28 days)
measure: Percentage of Participants With Grade 3 or Higher TEAEs
time frame: From first dose of study drug up to 28 days after the last dose of study drug or before the start of subsequent anticancer therapy (up to Cycle 31) (Cycle length =28 days)
description: TEAEs were graded as per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03. As per the NCI-CTCAE, Grade 1 (mild, asymptomatic or mild symptoms); Grade 2 (moderate, minimal, local or noninvasive intervention indicated); Grade 3 (severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated); Grade 4 (life-threatening consequences, urgent intervention indicated); Grade 5 (death related to adverse event [AE]).
measure: Percentage of Participants With Serious TEAEs
time frame: From first dose of study drug up to 28 days after the last dose of study drug or before the start of subsequent anticancer therapy (up to Cycle 31) (Cycle length =28 days)
measure: Dose Escalation Part: Percentage of Participants With Dose-limiting Toxicities (DLTs) During Cycle 1
time frame: Cycle 1 (Cycle length =28 days)
description: DLT was evaluated as per NCI-CTCAE, v4.03 and defined as any of the following events occurring during Cycle 1 that were considered by the investigator to be possibly related to therapy: Grade 4 neutropenia unresolved to less than or equal to (<=) Grade 1 or baseline for more than 7 days in the absence of growth factor support; greater than or equal to (>=) Grade 3 neutropenia with fever and/or infection;Grade 4 thrombocytopenia unresolved to <=Grade 1 or baseline for more than 7 days; >=Grade 3 thrombocytopenia with clinically significant bleeding; Grade >=3 nonhematologic toxicity except for treated >=Grade 3 nausea and/or emesis and diarrhea resolved to less than (<) Grade 3 within 3 days, Grade 3 fatigue <=72 hours, isolated asymptomatic >=Grade 3 laboratory abnormalities resolved to <=Grade 1 or baseline in <=7 days;received <75% of planned doses of study drug in Cycle 1;TAK-659-related >=Grade 2 nonhematologic toxicities that required dose reduction or discontinuation of therapy.
measure: Percentage of Participants Who Discontinued Study Drug Due to TEAEs
time frame: From first dose of study drug up to 28 days after the last dose of study drug or before the start of subsequent anticancer therapy (up to Cycle 31) (Cycle length =28 days)
measure: Cmax: Maximum Observed Plasma Concentration for TAK-659 on Cycle 1 Day 1
time frame: Cycle 1 Day 1: pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length= 28 days)
measure: Cmax: Maximum Observed Plasma Concentration for TAK-659 on Cycle 1 Day 7 (Dosing Schedule B) and Cycle 1 Day 15 (Dosing Schedule A)
time frame: Cycle 1 Day 7 (Dosing Schedule B) and Day 15 (Dosing Schedule A): pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length= 28 days)
measure: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-659 on Cycle 1 Day 1
time frame: Cycle 1 Day 1: pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length= 28 days)
measure: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-659 on Cycle 1 Day 7 (Dosing Schedule B) and Cycle 1 Day 15 (Dosing Schedule A)
time frame: Cycle 1 Day 7 (Dosing Schedule B) and Day 15 (Dosing Schedule A): pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length= 28 days)
measure: AUCτ: Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for TAK-659 on Cycle 1 Day 1
time frame: Cycle 1 Day 1: pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length= 28 days)
measure: AUCτ: Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for TAK-659 on Cycle 1 Day 7 (Dosing Schedule B) and Day 15 (Dosing Schedule A)
time frame: Cycle 1 Day 7 (Dosing Schedule B) and Day 15 (Dosing Schedule A): pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length= 28 days)
measure: CLR: Renal Clearance for TAK-659 on Cycle 1 Day 15
time frame: Cycle 1 Day 15: pre-dose and at multiple time points (up to 8 hours) post-dose (Cycle length= 28 days)
arm group label: Dose Escalation Part Schedule A: TAK-659 60 mg in Cohort 1
arm group type: Experimental
description: TAK-659, tablet, orally, once daily, in a 28-day treatment cycle for up to 12 months or until disease progression or unacceptable toxicity, with a starting dose of 60 milligram (mg) in Cohort 1. Dose escalation will follow a standard 3+3 schema . If 60 mg, once daily is safe and tolerable, then the dose will be escalated to 80 mg, once daily and subsequently in 20 mg increments until MTD and/or RP2D is determined. Based on emerging safety, tolerability, PK data, a lower dose will be permitted.
arm group label: Dose Escalation Part Schedule B: TAK-659 80 mg in Cohort 1
arm group type: Experimental
description: TAK-659, tablet, orally, once daily as 7 days on and 7 days off treatment (dosing on 7 days followed by 7 days of rest) in a 28-day treatment cycle for up to 12 months or until disease progression or unacceptable toxicity, with a starting dose of 80 mg in Cohort 1. Dose escalation will follow a standard 3+3 schema. An alternative intermittent regimen may be evaluated if deemed necessary per the emerging data.
arm group label: Expansion Part: TAK-659 MTD/RP2D
arm group type: Experimental
description: TAK-659, tablet, orally, once daily, in a 28-day treatment cycle until disease progression or unacceptable toxicity in participants with follicular lymphoma (FL) or marginal zone lymphoma (MZL) who are relapsed and/or refractory. Dose and dosing schedule for this part will be MTD/RP2D determined from results of dose escalation part.
intervention type: Drug
intervention name: TAK-659
description: TAK-659 Tablets.
arm group label: Dose Escalation Part Schedule A: TAK-659 60 mg in Cohort 1
arm group label: Dose Escalation Part Schedule B: TAK-659 80 mg in Cohort 1
arm group label: Expansion Part: TAK-659 MTD/RP2D
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Study Director
role: Study Director
affiliation: Takeda
facility: 
facility: 
facility: 
facility: 
country: Japan
country: Korea, Republic of
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Lymphoma, Non-Hodgkin
mesh term: Lymphoma, Follicular
sharing ipd: Yes
ipd description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd access criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
ipd url: https://vivli.org/ourmember/takeda/
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 