<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/NCT03261947</url>
  </required_header>
  <id_info>
    <org_study_id>TAK-931-2001</org_study_id>
    <secondary_id>U1111-1192-7975</secondary_id>
    <secondary_id>JapicCTI-163200</secondary_id>
    <nct_id>NCT03261947</nct_id>
  </id_info>
  <brief_title>A Study to Evaluate the Safety, Tolerability, and Activity of TAK-931 in Participants With Metastatic Pancreatic Cancer, Metastatic Colorectal Cancer, and Other Advanced Solid Tumors</brief_title>
  <official_title>An Open-Label, Phase 2, Parallel Arm Study to Evaluate the Safety, Tolerability, and Activity of TAK-931 Single Agent in Patients With Metastatic Pancreatic Cancer, Metastatic Colorectal Cancer, and Other Advanced Solid Tumors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Millennium Pharmaceuticals, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Takeda</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to confirm the safety and tolerability of TAK-931 in a cohort of&#xD;
      Western participants with metastatic solid tumors and to evaluate the anti-tumor activity of&#xD;
      TAK-931 in participants with metastatic pancreatic cancer, colorectal cancer (CRC), squamous&#xD;
      esophageal cancer (sqEC), and squamous non-small-cell lung cancer (sqNSCLC).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Pancreatic Arm Now Closed.&#xD;
&#xD;
      The drug being tested in this study is called TAK-931. TAK-931 blocks function of a specific&#xD;
      protein called CDC7 kinase in the human body. TAK-931 is being tested in participants with&#xD;
      metastatic cancer (colorectal, pancreatic, sqNSCLC and sqEC) in the United States and Japan&#xD;
      and also in the participants with any type of metastatic cancer with no standard therapeutic&#xD;
      alternative in the United States only. This study will look at the safety, tolerability and&#xD;
      pharmacokinetics of TAK-931.&#xD;
&#xD;
      The study will enroll approximately 160 participants. Participants will be enrolled in 5&#xD;
      cohorts: 1) Western safety cohort, to be enrolled in the United States only, will include&#xD;
      non-Japanese participants with metastatic solid tumors and no standard therapeutic&#xD;
      alternative, 2) Metastatic pancreatic cancer cohort, 3) Metastatic colorectal cancer cohort,&#xD;
      4) Metastatic sqNSCLC cohort, and 5) Metastatic sqEC cohort. All participants will receive:&#xD;
&#xD;
      • TAK-931 50 mg (2x25 mg or 5x10 mg) capsules&#xD;
&#xD;
      All participants will be asked to take one 50 mg (2x25 mg or 5x10 mg) capsule at the same&#xD;
      time of the day every day for 14 days, followed by 7 days break in 21-day cycles throughout&#xD;
      the study.&#xD;
&#xD;
      This multi-center trial will be conducted in the United States and Japan. The overall time to&#xD;
      participate in this study is approximately 24 months. Participants will make multiple visits&#xD;
      to the clinic. Participants in both Western cohort and disease specific cohorts will be&#xD;
      followed for progression-free survival every 12 weeks after the last dose of the study drug&#xD;
      until the occurrence of disease progression, loss to follow up, consent withdrawal, death,&#xD;
      start of subsequent antineoplastic therapy, study termination, or until 6 months after&#xD;
      discontinuation of the study treatment, whichever occurs first. Once disease progression is&#xD;
      confirmed, participants in the disease-specific cohorts will be followed for overall survival&#xD;
      every 12 weeks until death, loss to follow up, consent withdrawal, study termination, or&#xD;
      transfer of a participant to a long term safety study, single participant investigational new&#xD;
      drug application, or similar program after the last dose of the study drug.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 25, 2017</start_date>
  <completion_date type="Actual">August 24, 2020</completion_date>
  <primary_completion_date type="Actual">August 24, 2020</primary_completion_date>
  <phase>Phase 2</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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of Participants With Dose Limiting Toxicities (DLTs) in Western Safety Cohort</measure>
    <time_frame>Cycle 1 (each cycle = 21 days)</time_frame>
    <description>DLT:Any following event related to TAK-931 assessed by Common Terminology Criteria for Adverse Events(CTCAE) version4.03;Non-febrile Grade 4 neutropenia; febrile neutropenia: Grade &gt;=3 neutropenia; Grade4 thrombocytopenia; Grade &gt;=3 thrombocytopenia of any duration accompanied by Grade 2 bleeding or requiring transfusion; delay in initiation of Cycle 2 by &gt;14 days due to lack of adequate recovery of treatment-related hematological or nonhematologic toxicities; Grade 2 ejection fraction decreased by echocardiogram(ECHO) or multiple gated acquisition(MUGA) scan; Grade 4 laboratory abnormalities; other Grade 2 nonhematologic toxicities considered by investigator to be related to study drug and dose-limiting; Participants receiving &lt;50% of doses (&lt;7 doses) of planned TAK-931 dosing in Cycle 1 due to study drug-related adverse events(AEs); Grade &gt;=3 nonhematologic toxicity with few exceptions: Grade 3 arthralgia/myalgia, fatigue, laboratory abnormalities, nausea and/or emesis or diarrhea.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), TEAEs Leading to Dose Modifications and TEAEs Leading to Treatment Discontinuation in Western Safety Cohort</measure>
    <time_frame>From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months)</time_frame>
    <description>An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A TEAE was defined as an adverse event with an onset that occurred after receiving study drug. An SAE was any untoward medical occurrence or effect that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was medically important due to other reasons than the above mentioned criteria.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Disease Control Rate (DCR) in Tumor-Specific Cohorts</measure>
    <time_frame>From first dose up to end of treatment (Up to approximately 14 months)</time_frame>
    <description>DCR was defined as percentage of participants documented to have unconfirmed CR, PR, or SD for at least 6 weeks from treatment initiation according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) as the best response. CR was defined as disappearance of all lesions. PR was defined as at least a 30% decrease in the sum of the longest diameter (LD) of lesions, taking as reference the baseline sum LD. Stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum LD since the treatment started. PD was defined as at least a 20% increase in the sum of the LD of lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Cmax: Maximum Observed Plasma Concentration for TAK-931</measure>
    <time_frame>Cycle 1 (each cycle = 21 days) Days 1 and 8 pre-dose and at multiple timepoints (up to 24 hours) post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-931</measure>
    <time_frame>Cycle 1 (each cycle = 21 days) Days 1 and 8 pre-dose and at multiple timepoints (up to 24 hours) post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for TAK-931</measure>
    <time_frame>Cycle 1 (each cycle = 21 days) Days 1 and 8 pre-dose and at multiple timepoints (up to 24 hours) post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-931</measure>
    <time_frame>Cycle 1 (each cycle = 21 days) Days 1 and 8 pre-dose and at multiple timepoints (up to 24 hours) post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CLr: Renal Clearance of TAK-931</measure>
    <time_frame>Cycle 1 (each cycle = 21 days) Day 1 pre-dose and at multiple timepoints (up to 8 hours urine sampling) post-dose</time_frame>
    <description>CLr is a measure of apparent clearance of the drug from the plasma, renal clearance is a measure of drug excreted through kidneys/urine per unit time.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>t1/2z: Terminal Disposition Phase Half-life for TAK-931</measure>
    <time_frame>Cycle 1 (each cycle = 21 days) Day 8 pre-dose and at multiple timepoints (up to 24 hours) post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CLss/F: Steady-state Apparent Oral Clearance for TAK-931</measure>
    <time_frame>Cycle 1 (each cycle = 21 days) Day 8 pre-dose and at multiple timepoints (up to 24 hours) post-dose</time_frame>
    <description>CL/F was defined as apparent clearance of the drug from the plasma, calculated as the drug dose divided by AUC.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rac(AUC): Accumulation Ratio Based on AUC Over the Dosing Interval (AUCτ) for TAK-931</measure>
    <time_frame>Cycle 1 (each cycle = 21 days) Day 8 pre-dose and at multiple timepoints (up to 24 hours) post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Response Rate (CR and PR)</measure>
    <time_frame>From first dose up to end of treatment (Up to approximately 14 months)</time_frame>
    <description>Overall response rate was defined as percentage of participants documented to have unconfirmed CR or PR according to RECIST v1.1 as the best response. CR was defined as disappearance of all lesions, PR was defined as at least a 30% decrease in the sum of the LD of lesions, taking as reference the baseline sum LD.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (DOR)</measure>
    <time_frame>From first documented response until disease progression or end of treatment, whichever occurs first (Up to 14 months)</time_frame>
    <description>DOR was defined as the time from the date of first documentation of a CR or PR to the date of first documentation of tumor progression. Per RECIST V1.1, CR was defined as disappearance of all lesions, PR was defined as at least a 30% decrease in the sum of the LD of lesions, taking as reference the baseline sum LD. PD was defined as at least a 20% increase in the sum of the LD of lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival (PFS)</measure>
    <time_frame>From date of randomization until disease progression or death, whichever occurs first (Up to approximately 34 months)</time_frame>
    <description>PFS was defined as the time from the date of first dose to the date of first documentation of PD (including clinical progression or clinical deterioration) or death due to any cause, whichever occurs first. Per RECIST V1.1, PD was defined as at least a 20% increase in the sum of the LD of lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS) in the Tumor-Specific Cohorts</measure>
    <time_frame>Up to approximately 43 months</time_frame>
    <description>OS was defined as the time from the date of first dose of study drug to death due to any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Grade &gt;=3 TEAEs, SAEs, TEAEs Leading to Dose Modifications, and TEAEs Leading to Treatment Discontinuation in Tumor-Specific Cohorts</measure>
    <time_frame>From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months)</time_frame>
    <description>An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it did not necessarily have to have a causal relationship with this treatment. A TEAE was defined as an adverse event with an onset that occurred after receiving study drug. TEAEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.03, where 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 AE. An SAE was any untoward medical occurrence or effect that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was medically important due to other reasons than the above mentioned criteria.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts</measure>
    <time_frame>From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months)</time_frame>
    <description>Clinical laboratory tests included hematology, clinical chemistry and urinalysis. The investigator determined if the results were clinically significant. Only those categories were reported which are clinically significant at post Baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Clinically Significant Changes in Vital Sign Measurements, Reported as Adverse Events in Tumor-Specific Cohorts</measure>
    <time_frame>From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months)</time_frame>
    <description>Vital signs included assessments of systolic and diastolic blood pressure (BP), heart rate (HR), and body temperature. The investigator determined if the results were clinically significant. Only those categories were reported which are clinically significant at post Baseline.</description>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">101</enrollment>
  <condition>Metastatic Pancreatic Cancer</condition>
  <condition>Colorectal Cancer</condition>
  <condition>Esophageal Neoplasms</condition>
  <condition>Carcinoma, Non-small-cell Lung</condition>
  <arm_group>
    <arm_group_label>Western Safety Cohort</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, once daily (QD) for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 20 cycles. Participants with locally advanced or metastatic solid tumors with no standard therapeutic alternative in the United States were included in this cohort.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Pancreatic Cancer Cohort</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 4 cycles. Participants with metastatic pancreatic cancer who had progressed after at least 1 line of standard chemotherapy were included in this cohort.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Metastatic CRC Cohort</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 12 cycles. Participants with metastatic CRC who had progressed after at least 2 lines of previous standard chemotherapy were included in this cohort.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>sqEC Cohort</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 8 cycles. Participants with metastatic sqEC who had progressed after at least 1 line of standard chemotherapy were included in this cohort.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>sqNSCLC Cohort</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 18 cycles. Participants with metastatic sqNSCLC who had progressed after at least 2 lines of standard treatment were included in this cohort.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TAK-931</intervention_name>
    <description>TAK-931 hard gelatin capsules</description>
    <arm_group_label>Metastatic CRC Cohort</arm_group_label>
    <arm_group_label>Pancreatic Cancer Cohort</arm_group_label>
    <arm_group_label>Western Safety Cohort</arm_group_label>
    <arm_group_label>sqEC Cohort</arm_group_label>
    <arm_group_label>sqNSCLC Cohort</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Adult male or female participants aged &gt;=20 years (Japan) or &gt;=18 years (United&#xD;
             States).&#xD;
&#xD;
          2. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1&#xD;
&#xD;
          3. Has pathologically confirmed metastatic pancreatic adenocarcinoma that has progressed&#xD;
             after, at least, a first line of standard systemic chemotherapy for the metastatic&#xD;
             disease, OR participants with pathologically confirmed metastatic adenocarcinoma of&#xD;
             the colon or rectum who have progressed to at least 2 lines of standard systemic&#xD;
             chemotherapy for the metastatic disease, OR participants with pathologically confirmed&#xD;
             locally advanced or metastatic sqEC that has progressed after at least a first line of&#xD;
             standard systemic therapy for metastatic disease. First-line participants can be&#xD;
             enrolled if a platinum doublet is contraindicated or refused by the participants, OR&#xD;
             pathologically confirmed locally advanced or metastatic sqNSCLC that has progressed&#xD;
             after at least 2 lines of standard systemic therapy for metastatic disease.&#xD;
&#xD;
          4. For the Western safety cohort only: participants with locally advanced or metastatic&#xD;
             solid tumor for whom no standard treatment with an established survival benefit is&#xD;
             available or if the participant refuses other standard therapy.&#xD;
&#xD;
          5. For disease-specific cohort participants: measurable disease per RECIST v. 1.1&#xD;
&#xD;
          6. Left ventricular ejection fraction greater than (&gt;) 50% as measured by ECHO or MUGA&#xD;
             scan within 4 weeks before receiving the first dose of study drug.&#xD;
&#xD;
          7. Recovered to Grade 1 or baseline from all toxic effects of previous therapy (except&#xD;
             alopecia or neuropathy).&#xD;
&#xD;
          8. Suitable venous access for the study-required blood sampling.&#xD;
&#xD;
          9. For the Western safety cohort only: willingness to undergo serial skin tissue&#xD;
             biopsies.&#xD;
&#xD;
         10. For disease-specific cohort participants: Must have an archival (banked) tumor sample&#xD;
             or agree to have a new (fresh) tumor biopsy during the screening period. If a new&#xD;
             tumor sample is needed, the disease should be accessible for a nonsignificant risk&#xD;
             biopsy procedure (those occurring outside the brain, lung/mediastinum, and pancreas,&#xD;
             or obtained with endoscopic procedures not extending beyond the stomach or bowel). For&#xD;
             participants in the Western safety cohort, this biopsy is optional.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Participants who require continuous use of proton pump inhibitors (PPIs) or&#xD;
             histamine-2 (H2) receptor antagonists and participants who are taking PPIs within 5&#xD;
             days before the first dose of study drug.&#xD;
&#xD;
          2. Treatment with clinically significant enzyme inducers, such as phenytoin,&#xD;
             carbamazepine, phenobarbital, rifampin, rifabutin, rifapentine, or Saint John's wort&#xD;
             within 14 days before the first dose of study drug.&#xD;
&#xD;
          3. Treatment with any systemic anticancer treatment (including investigational products)&#xD;
             within 30 days or 5 half-lives, whichever is shorter, before the first dose of study&#xD;
             drug.&#xD;
&#xD;
          4. History of any of the following within the last 3 months before administration of the&#xD;
             first dose of study drug:&#xD;
&#xD;
               -  Ischemic myocardial event including angina requiring therapy and artery&#xD;
                  revascularization procedures, myocardial infarction, and unstable symptomatic&#xD;
                  ischemic heart disease.&#xD;
&#xD;
               -  Ischemic cerebrovascular event, including transient ischemic attack and artery,&#xD;
                  revascularization procedures.&#xD;
&#xD;
               -  Significant, uncontrolled cardiac arrhythmia (including atrial&#xD;
                  flutter/fibrillation, ventricular fibrillation, or ventricular tachycardia).&#xD;
&#xD;
               -  New York Heart Association Class III to IV heart failure.&#xD;
&#xD;
               -  Any other cardiac condition that, in the opinion of the investigator, could pose&#xD;
                  an additional risk for participation in the study (example, pericardial effusion&#xD;
                  or restrictive cardiomyopathy).&#xD;
&#xD;
               -  Baseline prolongation of the QT interval corrected for heart rate (HR) using&#xD;
                  Fridericia's formula [QT interval corrected for heart rate using Fridericia's&#xD;
                  formula (QTcF); example, repeated demonstration of QTcF interval &gt;480 millisecond&#xD;
                  (ms), history of congenital long QT syndrome, or torsades de pointes].&#xD;
&#xD;
          5. Hypertension that is unstable or not controlled by medication.&#xD;
&#xD;
          6. History of uncontrolled brain metastasis unless:&#xD;
&#xD;
               -  Previously treated with surgery, whole-brain radiation, or stereotactic&#xD;
                  radiosurgery, and&#xD;
&#xD;
               -  Stable disease (SD) for &gt;=30 days, without steroid use (or stable steroid dose&#xD;
                  established for &gt;=14 days before the first dose of TAK-931).&#xD;
&#xD;
          7. Known history of human immunodeficiency virus infection.&#xD;
&#xD;
          8. Known hepatitis B virus (HBV) surface antigen seropositive or detectable hepatitis C&#xD;
             virus (HCV) infection viral load. Note: Participants who have positive HBV core&#xD;
             antibody or HBV surface antigen antibody can be enrolled but must have an undetectable&#xD;
             HBV viral load.&#xD;
&#xD;
          9. Prior treatment with radiation therapy involving &gt;=25% of the hematopoietically active&#xD;
             bone marrow within 3 months before the first dose of study drug.&#xD;
&#xD;
         10. Participants with known microsatellite instability-high (MSI-H) genotype or known wild&#xD;
             type tumor protein 53 (TP53) per local testing.&#xD;
&#xD;
         11. Western Safety Cohort Only: Participants with Japanese heredity.&#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>Sarah Cannon Research Institute Oncology Research Consortium</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80218</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sarah Cannon Research Institute</name>
      <address>
        <city>Sarasota</city>
        <state>Florida</state>
        <zip>34232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Allina Health Virginia Piper Cancer Institute</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55404</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Siteman Cancer Center</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Comprehensive Cancer Centers of Nevada</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89119</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Oklahoma Health Sciences Center</name>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <zip>73104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SCRI - Tennessee Oncology - Nashville - Southern Hills Clinic</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Virginia Mason Medical Center</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98101-2756</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Cancer Center Hospital East</name>
      <address>
        <city>Kashiwa</city>
        <state>Chiba</state>
        <zip>277-8577</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_countries>
    <country>Japan</country>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2021</verification_date>
  <study_first_submitted>August 23, 2017</study_first_submitted>
  <study_first_submitted_qc>August 23, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 25, 2017</study_first_posted>
  <results_first_submitted>August 24, 2021</results_first_submitted>
  <results_first_submitted_qc>August 24, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">September 20, 2021</results_first_posted>
  <last_update_submitted>August 24, 2021</last_update_submitted>
  <last_update_submitted_qc>August 24, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">September 20, 2021</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>Colorectal Neoplasms</mesh_term>
    <mesh_term>Pancreatic Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Non-Small-Cell Lung</mesh_term>
    <mesh_term>Esophageal Neoplasms</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>July 16, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/47/NCT03261947/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>April 12, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/47/NCT03261947/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants took part in the study at 12 investigative sites in Japan and the United States from 25 October 2017 to 24 August 2020.</recruitment_details>
      <pre_assignment_details>The study had two parts, Part 1 (Safety Cohort) enrolled western participants with locally advanced/metastatic solid tumors to receive TAK-931 and assessed safety, tolerability and pharmacokinetics. In Part 2, participants were enrolled into Tumor (Disease)-Specific Cohorts based on tumor criteria: pancreatic cancer, metastatic colorectal cancer (CRC), squamous esophageal cancer (sqEC), squamous non-small-cell lung cancer (sqNSCLC) to receive TAK-931 and were assessed for antitumor activity.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Western Safety Cohort</title>
          <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, once daily (QD) for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 20 cycles. Participants with locally advanced or metastatic solid tumors with no standard therapeutic alternative in the United States were included in this cohort.</description>
        </group>
        <group group_id="P2">
          <title>Pancreatic Cancer Cohort</title>
          <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 4 cycles. Participants with metastatic pancreatic cancer who had progressed after at least 1 line of standard chemotherapy were included in this cohort.</description>
        </group>
        <group group_id="P3">
          <title>Metastatic CRC Cohort</title>
          <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 12 cycles. Participants with metastatic CRC who had progressed after at least 2 lines of previous standard chemotherapy were included in this cohort.</description>
        </group>
        <group group_id="P4">
          <title>sqEC Cohort</title>
          <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 8 cycles. Participants with metastatic sqEC who had progressed after at least 1 line of standard chemotherapy were included in this cohort.</description>
        </group>
        <group group_id="P5">
          <title>sqNSCLC Cohort</title>
          <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 18 cycles. Participants with metastatic sqNSCLC who had progressed after at least 2 lines of standard treatment were included in this cohort.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="15"/>
                <participants group_id="P3" count="35"/>
                <participants group_id="P4" count="21"/>
                <participants group_id="P5" count="18"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="5"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="13"/>
                <participants group_id="P3" count="30"/>
                <participants group_id="P4" count="21"/>
                <participants group_id="P5" count="17"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="13"/>
                <participants group_id="P3" count="17"/>
                <participants group_id="P4" count="12"/>
                <participants group_id="P5" count="8"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="2"/>
                <participants group_id="P4" count="1"/>
                <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="0"/>
                <participants group_id="P3" count="3"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Site Terminated by Sponsor</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="4"/>
                <participants group_id="P4" count="7"/>
                <participants group_id="P5" count="5"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Reason not Specified</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="4"/>
                <participants group_id="P4" count="1"/>
                <participants group_id="P5" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Safety Analysis Set included all participants who received any amount of study drug.</population>
      <group_list>
        <group group_id="B1">
          <title>Western Safety Cohort</title>
          <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, once daily (QD) for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 20 cycles. Participants with locally advanced or metastatic solid tumors with no standard therapeutic alternative in the United States were included in this cohort.</description>
        </group>
        <group group_id="B2">
          <title>Pancreatic Cancer Cohort</title>
          <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 4 cycles. Participants with metastatic pancreatic cancer who had progressed after at least 1 line of standard chemotherapy were included in this cohort.</description>
        </group>
        <group group_id="B3">
          <title>Metastatic CRC Cohort</title>
          <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 12 cycles. Participants with metastatic CRC who had progressed after at least 2 lines of previous standard chemotherapy were included in this cohort.</description>
        </group>
        <group group_id="B4">
          <title>sqEC Cohort</title>
          <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 8 cycles. Participants with metastatic sqEC who had progressed after at least 1 line of standard chemotherapy were included in this cohort.</description>
        </group>
        <group group_id="B5">
          <title>sqNSCLC Cohort</title>
          <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 18 cycles. Participants with metastatic sqNSCLC who had progressed after at least 2 lines of standard treatment were included in this cohort.</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="12"/>
            <count group_id="B2" value="15"/>
            <count group_id="B3" value="35"/>
            <count group_id="B4" value="21"/>
            <count group_id="B5" value="18"/>
            <count group_id="B6" value="101"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="12"/>
                    <count group_id="B2" value="15"/>
                    <count group_id="B3" value="35"/>
                    <count group_id="B4" value="21"/>
                    <count group_id="B5" value="18"/>
                    <count group_id="B6" value="101"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="59.3" spread="7.16"/>
                    <measurement group_id="B2" value="63.1" spread="12.27"/>
                    <measurement group_id="B3" value="58.3" spread="11.93"/>
                    <measurement group_id="B4" value="64.2" spread="7.71"/>
                    <measurement group_id="B5" value="64.4" spread="7.74"/>
                    <measurement group_id="B6" value="61.5" spread="10.23"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="12"/>
                    <count group_id="B2" value="15"/>
                    <count group_id="B3" value="35"/>
                    <count group_id="B4" value="21"/>
                    <count group_id="B5" value="18"/>
                    <count group_id="B6" value="101"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="19"/>
                    <measurement group_id="B4" value="4"/>
                    <measurement group_id="B5" value="7"/>
                    <measurement group_id="B6" value="40"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="16"/>
                    <measurement group_id="B4" value="17"/>
                    <measurement group_id="B5" value="11"/>
                    <measurement group_id="B6" value="61"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="12"/>
                    <count group_id="B2" value="15"/>
                    <count group_id="B3" value="35"/>
                    <count group_id="B4" value="21"/>
                    <count group_id="B5" value="18"/>
                    <count group_id="B6" value="101"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="34"/>
                    <measurement group_id="B4" value="21"/>
                    <measurement group_id="B5" value="18"/>
                    <measurement group_id="B6" value="96"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="3"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="12"/>
                    <count group_id="B2" value="15"/>
                    <count group_id="B3" value="35"/>
                    <count group_id="B4" value="21"/>
                    <count group_id="B5" value="18"/>
                    <count group_id="B6" value="101"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <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="0"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="8"/>
                    <measurement group_id="B4" value="16"/>
                    <measurement group_id="B5" value="2"/>
                    <measurement group_id="B6" value="29"/>
                  </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="3"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="1"/>
                    <measurement group_id="B6" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="24"/>
                    <measurement group_id="B4" value="4"/>
                    <measurement group_id="B5" value="15"/>
                    <measurement group_id="B6" value="64"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="12"/>
                    <count group_id="B2" value="15"/>
                    <count group_id="B3" value="35"/>
                    <count group_id="B4" value="21"/>
                    <count group_id="B5" value="18"/>
                    <count group_id="B6" value="101"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="8"/>
                    <measurement group_id="B4" value="16"/>
                    <measurement group_id="B5" value="2"/>
                    <measurement group_id="B6" value="29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>United States</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="12"/>
                    <count group_id="B2" value="15"/>
                    <count group_id="B3" value="35"/>
                    <count group_id="B4" value="21"/>
                    <count group_id="B5" value="18"/>
                    <count group_id="B6" value="101"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="27"/>
                    <measurement group_id="B4" value="5"/>
                    <measurement group_id="B5" value="16"/>
                    <measurement group_id="B6" value="72"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Height</title>
          <population>Number analyzed is the number of participants with data available for height at the Baseline.</population>
          <units>cm</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="12"/>
                    <count group_id="B2" value="15"/>
                    <count group_id="B3" value="34"/>
                    <count group_id="B4" value="20"/>
                    <count group_id="B5" value="18"/>
                    <count group_id="B6" value="99"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="172.47" spread="13.371"/>
                    <measurement group_id="B2" value="170.61" spread="11.596"/>
                    <measurement group_id="B3" value="168.64" spread="10.203"/>
                    <measurement group_id="B4" value="167.11" spread="7.975"/>
                    <measurement group_id="B5" value="172.26" spread="10.693"/>
                    <measurement group_id="B6" value="169.75" spread="10.513"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Weight</title>
          <population>Number analyzed is the number of participants with data available for weight at the Baseline.</population>
          <units>kg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="12"/>
                    <count group_id="B2" value="15"/>
                    <count group_id="B3" value="35"/>
                    <count group_id="B4" value="20"/>
                    <count group_id="B5" value="18"/>
                    <count group_id="B6" value="100"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="79.33" spread="16.052"/>
                    <measurement group_id="B2" value="73.22" spread="22.763"/>
                    <measurement group_id="B3" value="79.90" spread="17.457"/>
                    <measurement group_id="B4" value="57.07" spread="10.358"/>
                    <measurement group_id="B5" value="77.70" spread="18.770"/>
                    <measurement group_id="B6" value="73.87" spread="19.076"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Substance Use</title>
          <population>Data for substance use was collected only for sqEC and sqNSCLC cohorts. Number analyzed is the number of participants with data available for substance use at Baseline.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="0"/>
                    <count group_id="B4" value="20"/>
                    <count group_id="B5" value="18"/>
                    <count group_id="B6" value="38"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Tobacco</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="12"/>
                    <measurement group_id="B5" value="3"/>
                    <measurement group_id="B6" value="15"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Cigarette</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="6"/>
                    <measurement group_id="B5" value="15"/>
                    <measurement group_id="B6" value="21"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Cigar</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="1"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Pipe</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="1"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Smoking Classification</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="12"/>
                    <count group_id="B2" value="15"/>
                    <count group_id="B3" value="35"/>
                    <count group_id="B4" value="21"/>
                    <count group_id="B5" value="18"/>
                    <count group_id="B6" value="101"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Never Smoked</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="35"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="1"/>
                    <measurement group_id="B6" value="65"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Current Smoker</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="3"/>
                    <measurement group_id="B5" value="7"/>
                    <measurement group_id="B6" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Former Smoker</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="16"/>
                    <measurement group_id="B5" value="10"/>
                    <measurement group_id="B6" value="26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Participants With Dose Limiting Toxicities (DLTs) in Western Safety Cohort</title>
        <description>DLT:Any following event related to TAK-931 assessed by Common Terminology Criteria for Adverse Events(CTCAE) version4.03;Non-febrile Grade 4 neutropenia; febrile neutropenia: Grade &gt;=3 neutropenia; Grade4 thrombocytopenia; Grade &gt;=3 thrombocytopenia of any duration accompanied by Grade 2 bleeding or requiring transfusion; delay in initiation of Cycle 2 by &gt;14 days due to lack of adequate recovery of treatment-related hematological or nonhematologic toxicities; Grade 2 ejection fraction decreased by echocardiogram(ECHO) or multiple gated acquisition(MUGA) scan; Grade 4 laboratory abnormalities; other Grade 2 nonhematologic toxicities considered by investigator to be related to study drug and dose-limiting; Participants receiving &lt;50% of doses (&lt;7 doses) of planned TAK-931 dosing in Cycle 1 due to study drug-related adverse events(AEs); Grade &gt;=3 nonhematologic toxicity with few exceptions: Grade 3 arthralgia/myalgia, fatigue, laboratory abnormalities, nausea and/or emesis or diarrhea.</description>
        <time_frame>Cycle 1 (each cycle = 21 days)</time_frame>
        <population>DLT-evaluable Analysis Set included all participants in the Western Safety Cohort who received at least 1 of their planned TAK-931 doses during their first cycle of treatment (unless interrupted by related AEs) and who had sufficient follow-up data to allow the investigators and sponsor to determine whether a DLT occurred. As pre-specified in the protocol, DLTs were collected only from participants in the Western Safety Cohort who were evaluable in DLT-evaluable Analysis Set.</population>
        <group_list>
          <group group_id="O1">
            <title>Western Safety Cohort</title>
            <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, once daily (QD) for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 20 cycles. Participants with locally advanced or metastatic solid tumors with no standard therapeutic alternative in the United States were included in this cohort.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Dose Limiting Toxicities (DLTs) in Western Safety Cohort</title>
          <description>DLT:Any following event related to TAK-931 assessed by Common Terminology Criteria for Adverse Events(CTCAE) version4.03;Non-febrile Grade 4 neutropenia; febrile neutropenia: Grade &gt;=3 neutropenia; Grade4 thrombocytopenia; Grade &gt;=3 thrombocytopenia of any duration accompanied by Grade 2 bleeding or requiring transfusion; delay in initiation of Cycle 2 by &gt;14 days due to lack of adequate recovery of treatment-related hematological or nonhematologic toxicities; Grade 2 ejection fraction decreased by echocardiogram(ECHO) or multiple gated acquisition(MUGA) scan; Grade 4 laboratory abnormalities; other Grade 2 nonhematologic toxicities considered by investigator to be related to study drug and dose-limiting; Participants receiving &lt;50% of doses (&lt;7 doses) of planned TAK-931 dosing in Cycle 1 due to study drug-related adverse events(AEs); Grade &gt;=3 nonhematologic toxicity with few exceptions: Grade 3 arthralgia/myalgia, fatigue, laboratory abnormalities, nausea and/or emesis or diarrhea.</description>
          <population>DLT-evaluable Analysis Set included all participants in the Western Safety Cohort who received at least 1 of their planned TAK-931 doses during their first cycle of treatment (unless interrupted by related AEs) and who had sufficient follow-up data to allow the investigators and sponsor to determine whether a DLT occurred. As pre-specified in the protocol, DLTs were collected only from participants in the Western Safety Cohort who were evaluable in DLT-evaluable Analysis Set.</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="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), TEAEs Leading to Dose Modifications and TEAEs Leading to Treatment Discontinuation in Western Safety Cohort</title>
        <description>An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A TEAE was defined as an adverse event with an onset that occurred after receiving study drug. An SAE was any untoward medical occurrence or effect that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was medically important due to other reasons than the above mentioned criteria.</description>
        <time_frame>From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months)</time_frame>
        <population>Safety Analysis Set included all participants who received any amount of study drug. As pre-specified in the protocol, this outcome measure reports data only in the participants with locally advanced or metastatic solid tumors in the Western Safety Cohort.</population>
        <group_list>
          <group group_id="O1">
            <title>Western Safety Cohort</title>
            <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, once daily (QD) for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 20 cycles. Participants with locally advanced or metastatic solid tumors with no standard therapeutic alternative in the United States were included in this cohort.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), TEAEs Leading to Dose Modifications and TEAEs Leading to Treatment Discontinuation in Western Safety Cohort</title>
          <description>An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A TEAE was defined as an adverse event with an onset that occurred after receiving study drug. An SAE was any untoward medical occurrence or effect that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was medically important due to other reasons than the above mentioned criteria.</description>
          <population>Safety Analysis Set included all participants who received any amount of study drug. As pre-specified in the protocol, this outcome measure reports data only in the participants with locally advanced or metastatic solid tumors in the Western Safety Cohort.</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="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>TEAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="58.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEAEs Leading to Dose Modifications</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEAEs Leading to Treatment Discontinuation</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Disease Control Rate (DCR) in Tumor-Specific Cohorts</title>
        <description>DCR was defined as percentage of participants documented to have unconfirmed CR, PR, or SD for at least 6 weeks from treatment initiation according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) as the best response. CR was defined as disappearance of all lesions. PR was defined as at least a 30% decrease in the sum of the longest diameter (LD) of lesions, taking as reference the baseline sum LD. Stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum LD since the treatment started. PD was defined as at least a 20% increase in the sum of the LD of lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.</description>
        <time_frame>From first dose up to end of treatment (Up to approximately 14 months)</time_frame>
        <population>Response-evaluable Analysis Set included all participants who received at least 1 dose of study drug, had measurable disease at Baseline, and had at least 1 post-baseline response assessment. As pre-specified in the protocol, this outcome measure evaluated and reported data for participants only in the Tumor-Specific Cohorts.</population>
        <group_list>
          <group group_id="O1">
            <title>Pancreatic Cancer Cohort</title>
            <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 4 cycles. Participants with metastatic pancreatic cancer who had progressed after at least 1 line of standard chemotherapy were included in this cohort.</description>
          </group>
          <group group_id="O2">
            <title>Metastatic CRC Cohort</title>
            <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 12 cycles. Participants with metastatic CRC who had progressed after at least 2 lines of previous standard chemotherapy were included in this cohort.</description>
          </group>
          <group group_id="O3">
            <title>sqEC Cohort</title>
            <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 8 cycles. Participants with metastatic sqEC who had progressed after at least 1 line of standard chemotherapy were included in this cohort.</description>
          </group>
          <group group_id="O4">
            <title>sqNSCLC Cohort</title>
            <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 18 cycles. Participants with metastatic sqNSCLC who had progressed after at least 2 lines of standard treatment were included in this cohort.</description>
          </group>
        </group_list>
        <measure>
          <title>Disease Control Rate (DCR) in Tumor-Specific Cohorts</title>
          <description>DCR was defined as percentage of participants documented to have unconfirmed CR, PR, or SD for at least 6 weeks from treatment initiation according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) as the best response. CR was defined as disappearance of all lesions. PR was defined as at least a 30% decrease in the sum of the longest diameter (LD) of lesions, taking as reference the baseline sum LD. Stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum LD since the treatment started. PD was defined as at least a 20% increase in the sum of the LD of lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.</description>
          <population>Response-evaluable Analysis Set included all participants who received at least 1 dose of study drug, had measurable disease at Baseline, and had at least 1 post-baseline response assessment. As pre-specified in the protocol, this outcome measure evaluated and reported data for participants only in the Tumor-Specific Cohorts.</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="13"/>
                <count group_id="O2" value="31"/>
                <count group_id="O3" value="19"/>
                <count group_id="O4" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="46.2" lower_limit="26.4" upper_limit="66.9"/>
                    <measurement group_id="O2" value="51.6" lower_limit="38.7" upper_limit="64.3"/>
                    <measurement group_id="O3" value="52.6" lower_limit="35.8" upper_limit="69.0"/>
                    <measurement group_id="O4" value="58.8" lower_limit="40.6" upper_limit="75.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cmax: Maximum Observed Plasma Concentration for TAK-931</title>
        <time_frame>Cycle 1 (each cycle = 21 days) Days 1 and 8 pre-dose and at multiple timepoints (up to 24 hours) post-dose</time_frame>
        <population>Pharmacokinetic (PK) Analysis Set included all participants for whom there was sufficient dosing and TAK-931 concentration-time data to reliably estimate the PK parameters. As prespecified in the protocol, data for intensive PK sampling was collected only for participants in Western Safety Cohort, Pancreatic Cancer Cohort, and Metastatic CRC Cohort. Number analyzed is the number of participants with data available for analysis at the given timepoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Western Safety Cohort</title>
            <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, once daily (QD) for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 20 cycles. Participants with locally advanced or metastatic solid tumors with no standard therapeutic alternative in the United States were included in this cohort.</description>
          </group>
          <group group_id="O2">
            <title>Pancreatic Cancer Cohort</title>
            <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 4 cycles. Participants with metastatic pancreatic cancer who had progressed after at least 1 line of standard chemotherapy were included in this cohort.</description>
          </group>
          <group group_id="O3">
            <title>Metastatic CRC Cohort</title>
            <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 12 cycles. Participants with metastatic CRC who had progressed after at least 2 lines of previous standard chemotherapy were included in this cohort.</description>
          </group>
        </group_list>
        <measure>
          <title>Cmax: Maximum Observed Plasma Concentration for TAK-931</title>
          <population>Pharmacokinetic (PK) Analysis Set included all participants for whom there was sufficient dosing and TAK-931 concentration-time data to reliably estimate the PK parameters. As prespecified in the protocol, data for intensive PK sampling was collected only for participants in Western Safety Cohort, Pancreatic Cancer Cohort, and Metastatic CRC Cohort. Number analyzed is the number of participants with data available for analysis at the given timepoint.</population>
          <units>ng/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="15"/>
                <count group_id="O3" value="34"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle 1 Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="12"/>
                    <count group_id="O2" value="12"/>
                    <count group_id="O3" value="13"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="173.61" spread="59.677"/>
                    <measurement group_id="O2" value="204.69" spread="90.527"/>
                    <measurement group_id="O3" value="185.46" spread="61.158"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 1 Day 8</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="12"/>
                    <count group_id="O2" value="10"/>
                    <count group_id="O3" value="11"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="196.17" spread="73.702"/>
                    <measurement group_id="O2" value="180.55" spread="75.036"/>
                    <measurement group_id="O3" value="216.18" spread="121.488"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-931</title>
        <time_frame>Cycle 1 (each cycle = 21 days) Days 1 and 8 pre-dose and at multiple timepoints (up to 24 hours) post-dose</time_frame>
        <population>PK Analysis Set included all participants for whom there was sufficient dosing and TAK-931 concentration-time data to reliably estimate the PK parameters. As prespecified in the protocol, data for intensive PK sampling was collected only for participants in Western Safety Cohort, Pancreatic Cancer Cohort, and Metastatic CRC Cohort. Number analyzed is the number of participants with data available for analysis at the given timepoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Western Safety Cohort</title>
            <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, once daily (QD) for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 20 cycles. Participants with locally advanced or metastatic solid tumors with no standard therapeutic alternative in the United States were included in this cohort.</description>
          </group>
          <group group_id="O2">
            <title>Pancreatic Cancer Cohort</title>
            <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 4 cycles. Participants with metastatic pancreatic cancer who had progressed after at least 1 line of standard chemotherapy were included in this cohort.</description>
          </group>
          <group group_id="O3">
            <title>Metastatic CRC Cohort</title>
            <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 12 cycles. Participants with metastatic CRC who had progressed after at least 2 lines of previous standard chemotherapy were included in this cohort.</description>
          </group>
        </group_list>
        <measure>
          <title>Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-931</title>
          <population>PK Analysis Set included all participants for whom there was sufficient dosing and TAK-931 concentration-time data to reliably estimate the PK parameters. As prespecified in the protocol, data for intensive PK sampling was collected only for participants in Western Safety Cohort, Pancreatic Cancer Cohort, and Metastatic CRC Cohort. Number analyzed is the number of participants with data available for analysis at the given timepoint.</population>
          <units>hour</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="15"/>
                <count group_id="O3" value="34"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle 1 Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="12"/>
                    <count group_id="O2" value="12"/>
                    <count group_id="O3" value="13"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.57" lower_limit="0.8" upper_limit="2.2"/>
                    <measurement group_id="O2" value="2.00" lower_limit="0.5" upper_limit="6.3"/>
                    <measurement group_id="O3" value="1.85" lower_limit="0.9" upper_limit="6.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 1 Day 8</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="12"/>
                    <count group_id="O2" value="10"/>
                    <count group_id="O3" value="11"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.59" lower_limit="1.0" upper_limit="4.0"/>
                    <measurement group_id="O2" value="2.00" lower_limit="1.0" upper_limit="4.3"/>
                    <measurement group_id="O3" value="1.97" lower_limit="1.0" upper_limit="4.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for TAK-931</title>
        <time_frame>Cycle 1 (each cycle = 21 days) Days 1 and 8 pre-dose and at multiple timepoints (up to 24 hours) post-dose</time_frame>
        <population>PK Analysis Set included all participants for whom there was sufficient dosing and TAK-931 concentration-time data to reliably estimate the PK parameters. As prespecified in the protocol, data for intensive PK sampling was collected only for participants in Western Safety Cohort, Pancreatic Cancer Cohort, and Metastatic CRC Cohort. Number analyzed is the number of participants with data available for analysis at the given timepoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Western Safety Cohort</title>
            <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, once daily (QD) for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 20 cycles. Participants with locally advanced or metastatic solid tumors with no standard therapeutic alternative in the United States were included in this cohort.</description>
          </group>
          <group group_id="O2">
            <title>Pancreatic Cancer Cohort</title>
            <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 4 cycles. Participants with metastatic pancreatic cancer who had progressed after at least 1 line of standard chemotherapy were included in this cohort.</description>
          </group>
          <group group_id="O3">
            <title>Metastatic CRC Cohort</title>
            <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 12 cycles. Participants with metastatic CRC who had progressed after at least 2 lines of previous standard chemotherapy were included in this cohort.</description>
          </group>
        </group_list>
        <measure>
          <title>AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for TAK-931</title>
          <population>PK Analysis Set included all participants for whom there was sufficient dosing and TAK-931 concentration-time data to reliably estimate the PK parameters. As prespecified in the protocol, data for intensive PK sampling was collected only for participants in Western Safety Cohort, Pancreatic Cancer Cohort, and Metastatic CRC Cohort. Number analyzed is the number of participants with data available for analysis at the given timepoint.</population>
          <units>h*ng/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="15"/>
                <count group_id="O3" value="34"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle 1 Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="12"/>
                    <count group_id="O2" value="12"/>
                    <count group_id="O3" value="13"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1190.22" spread="540.877"/>
                    <measurement group_id="O2" value="1166.40" spread="362.856"/>
                    <measurement group_id="O3" value="1302.40" spread="391.035"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 1 Day 8</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="11"/>
                    <count group_id="O2" value="10"/>
                    <count group_id="O3" value="11"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1475.88" spread="749.707"/>
                    <measurement group_id="O2" value="1290.72" spread="615.542"/>
                    <measurement group_id="O3" value="1542.82" spread="507.733"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-931</title>
        <time_frame>Cycle 1 (each cycle = 21 days) Days 1 and 8 pre-dose and at multiple timepoints (up to 24 hours) post-dose</time_frame>
        <population>PK Analysis Set included all participants for whom there was sufficient dosing and TAK-931 concentration-time data to reliably estimate the PK parameters. As prespecified in the protocol, data for intensive PK sampling was collected only for participants in Western Safety Cohort, Pancreatic Cancer Cohort, and Metastatic CRC Cohort. Number analyzed is the number of participants with data available for analysis at the given timepoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Western Safety Cohort</title>
            <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, once daily (QD) for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 20 cycles. Participants with locally advanced or metastatic solid tumors with no standard therapeutic alternative in the United States were included in this cohort.</description>
          </group>
          <group group_id="O2">
            <title>Pancreatic Cancer Cohort</title>
            <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 4 cycles. Participants with metastatic pancreatic cancer who had progressed after at least 1 line of standard chemotherapy were included in this cohort.</description>
          </group>
          <group group_id="O3">
            <title>Metastatic CRC Cohort</title>
            <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 12 cycles. Participants with metastatic CRC who had progressed after at least 2 lines of previous standard chemotherapy were included in this cohort.</description>
          </group>
        </group_list>
        <measure>
          <title>AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-931</title>
          <population>PK Analysis Set included all participants for whom there was sufficient dosing and TAK-931 concentration-time data to reliably estimate the PK parameters. As prespecified in the protocol, data for intensive PK sampling was collected only for participants in Western Safety Cohort, Pancreatic Cancer Cohort, and Metastatic CRC Cohort. Number analyzed is the number of participants with data available for analysis at the given timepoint.</population>
          <units>h*ng/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="15"/>
                <count group_id="O3" value="34"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle 1 Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="12"/>
                    <count group_id="O2" value="12"/>
                    <count group_id="O3" value="13"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1165.52" spread="552.287"/>
                    <measurement group_id="O2" value="1114.23" spread="388.844"/>
                    <measurement group_id="O3" value="1311.41" spread="388.557"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 1 Day 8</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="12"/>
                    <count group_id="O2" value="10"/>
                    <count group_id="O3" value="11"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1426.70" spread="774.257"/>
                    <measurement group_id="O2" value="1289.33" spread="616.737"/>
                    <measurement group_id="O3" value="1551.57" spread="497.856"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>CLr: Renal Clearance of TAK-931</title>
        <description>CLr is a measure of apparent clearance of the drug from the plasma, renal clearance is a measure of drug excreted through kidneys/urine per unit time.</description>
        <time_frame>Cycle 1 (each cycle = 21 days) Day 1 pre-dose and at multiple timepoints (up to 8 hours urine sampling) post-dose</time_frame>
        <population>PK Analysis Set included all participants for whom there was sufficient dosing and TAK-931 concentration-time data to reliably estimate the PK parameters. As prespecified in the protocol, data for urine PK sampling was collected only for participants in Western Safety Cohort. Overall number of participants analyzed are the number of participants with data available for analyses.</population>
        <group_list>
          <group group_id="O1">
            <title>Western Safety Cohort</title>
            <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, once daily (QD) for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 20 cycles. Participants with locally advanced or metastatic solid tumors with no standard therapeutic alternative in the United States were included in this cohort.</description>
          </group>
        </group_list>
        <measure>
          <title>CLr: Renal Clearance of TAK-931</title>
          <description>CLr is a measure of apparent clearance of the drug from the plasma, renal clearance is a measure of drug excreted through kidneys/urine per unit time.</description>
          <population>PK Analysis Set included all participants for whom there was sufficient dosing and TAK-931 concentration-time data to reliably estimate the PK parameters. As prespecified in the protocol, data for urine PK sampling was collected only for participants in Western Safety Cohort. Overall number of participants analyzed are the number of participants with data available for analyses.</population>
          <units>L/h</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.16" spread="1.913"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>t1/2z: Terminal Disposition Phase Half-life for TAK-931</title>
        <time_frame>Cycle 1 (each cycle = 21 days) Day 8 pre-dose and at multiple timepoints (up to 24 hours) post-dose</time_frame>
        <population>PK Analysis Set included all participants for whom there was sufficient dosing and TAK-931 concentration-time data to reliably estimate the PK parameters. As prespecified in the protocol, data for intensive PK sampling was collected only for participants in Western Safety Cohort, Pancreatic Cancer Cohort, and Metastatic CRC Cohort. Overall number of participants analyzed are the number of participants with data available for analyses.</population>
        <group_list>
          <group group_id="O1">
            <title>Western Safety Cohort</title>
            <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, once daily (QD) for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 20 cycles. Participants with locally advanced or metastatic solid tumors with no standard therapeutic alternative in the United States were included in this cohort.</description>
          </group>
          <group group_id="O2">
            <title>Pancreatic Cancer Cohort</title>
            <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 4 cycles. Participants with metastatic pancreatic cancer who had progressed after at least 1 line of standard chemotherapy were included in this cohort.</description>
          </group>
          <group group_id="O3">
            <title>Metastatic CRC Cohort</title>
            <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 12 cycles. Participants with metastatic CRC who had progressed after at least 2 lines of previous standard chemotherapy were included in this cohort.</description>
          </group>
        </group_list>
        <measure>
          <title>t1/2z: Terminal Disposition Phase Half-life for TAK-931</title>
          <population>PK Analysis Set included all participants for whom there was sufficient dosing and TAK-931 concentration-time data to reliably estimate the PK parameters. As prespecified in the protocol, data for intensive PK sampling was collected only for participants in Western Safety Cohort, Pancreatic Cancer Cohort, and Metastatic CRC Cohort. Overall number of participants analyzed are the number of participants with data available for analyses.</population>
          <units>hour</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
                <count group_id="O2" value="10"/>
                <count group_id="O3" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.95" lower_limit="4.3" upper_limit="6.7"/>
                    <measurement group_id="O2" value="5.53" lower_limit="3.7" upper_limit="8.0"/>
                    <measurement group_id="O3" value="6.18" lower_limit="4.8" upper_limit="8.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>CLss/F: Steady-state Apparent Oral Clearance for TAK-931</title>
        <description>CL/F was defined as apparent clearance of the drug from the plasma, calculated as the drug dose divided by AUC.</description>
        <time_frame>Cycle 1 (each cycle = 21 days) Day 8 pre-dose and at multiple timepoints (up to 24 hours) post-dose</time_frame>
        <population>PK Analysis Set included all participants for whom there was sufficient dosing and TAK-931 concentration-time data to reliably estimate the PK parameters. As prespecified in the protocol, data for intensive PK sampling was collected only for participants in Western Safety Cohort, Pancreatic Cancer Cohort, and Metastatic CRC Cohort. Overall number of participants analyzed are the number of participants with data available for analyses.</population>
        <group_list>
          <group group_id="O1">
            <title>Western Safety Cohort</title>
            <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, once daily (QD) for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 20 cycles. Participants with locally advanced or metastatic solid tumors with no standard therapeutic alternative in the United States were included in this cohort.</description>
          </group>
          <group group_id="O2">
            <title>Pancreatic Cancer Cohort</title>
            <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 4 cycles. Participants with metastatic pancreatic cancer who had progressed after at least 1 line of standard chemotherapy were included in this cohort.</description>
          </group>
          <group group_id="O3">
            <title>Metastatic CRC Cohort</title>
            <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 12 cycles. Participants with metastatic CRC who had progressed after at least 2 lines of previous standard chemotherapy were included in this cohort.</description>
          </group>
        </group_list>
        <measure>
          <title>CLss/F: Steady-state Apparent Oral Clearance for TAK-931</title>
          <description>CL/F was defined as apparent clearance of the drug from the plasma, calculated as the drug dose divided by AUC.</description>
          <population>PK Analysis Set included all participants for whom there was sufficient dosing and TAK-931 concentration-time data to reliably estimate the PK parameters. As prespecified in the protocol, data for intensive PK sampling was collected only for participants in Western Safety Cohort, Pancreatic Cancer Cohort, and Metastatic CRC Cohort. Overall number of participants analyzed are the number of participants with data available for analyses.</population>
          <units>L/h</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
                <count group_id="O2" value="10"/>
                <count group_id="O3" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="39.71" spread="14.135"/>
                    <measurement group_id="O2" value="45.58" spread="18.877"/>
                    <measurement group_id="O3" value="35.57" spread="10.778"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Rac(AUC): Accumulation Ratio Based on AUC Over the Dosing Interval (AUCτ) for TAK-931</title>
        <time_frame>Cycle 1 (each cycle = 21 days) Day 8 pre-dose and at multiple timepoints (up to 24 hours) post-dose</time_frame>
        <population>PK Analysis Set included all participants for whom there was sufficient dosing and TAK-931 concentration-time data to reliably estimate the PK parameters. As prespecified in the protocol, data for intensive PK sampling was collected only for participants in Western Safety Cohort, Pancreatic Cancer Cohort, and Metastatic CRC Cohort. Overall number of participants analyzed are the number of participants with data available for analyses.</population>
        <group_list>
          <group group_id="O1">
            <title>Western Safety Cohort</title>
            <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, once daily (QD) for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 20 cycles. Participants with locally advanced or metastatic solid tumors with no standard therapeutic alternative in the United States were included in this cohort.</description>
          </group>
          <group group_id="O2">
            <title>Pancreatic Cancer Cohort</title>
            <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 4 cycles. Participants with metastatic pancreatic cancer who had progressed after at least 1 line of standard chemotherapy were included in this cohort.</description>
          </group>
          <group group_id="O3">
            <title>Metastatic CRC Cohort</title>
            <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 12 cycles. Participants with metastatic CRC who had progressed after at least 2 lines of previous standard chemotherapy were included in this cohort.</description>
          </group>
        </group_list>
        <measure>
          <title>Rac(AUC): Accumulation Ratio Based on AUC Over the Dosing Interval (AUCτ) for TAK-931</title>
          <population>PK Analysis Set included all participants for whom there was sufficient dosing and TAK-931 concentration-time data to reliably estimate the PK parameters. As prespecified in the protocol, data for intensive PK sampling was collected only for participants in Western Safety Cohort, Pancreatic Cancer Cohort, and Metastatic CRC Cohort. Overall number of participants analyzed are the number of participants with data available for analyses.</population>
          <units>ratio</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
                <count group_id="O2" value="10"/>
                <count group_id="O3" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.27" spread="0.317"/>
                    <measurement group_id="O2" value="1.10" spread="0.299"/>
                    <measurement group_id="O3" value="1.12" spread="0.203"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Response Rate (CR and PR)</title>
        <description>Overall response rate was defined as percentage of participants documented to have unconfirmed CR or PR according to RECIST v1.1 as the best response. CR was defined as disappearance of all lesions, PR was defined as at least a 30% decrease in the sum of the LD of lesions, taking as reference the baseline sum LD.</description>
        <time_frame>From first dose up to end of treatment (Up to approximately 14 months)</time_frame>
        <population>Response-evaluable Analysis Set included all participants who received at least 1 dose of study drug, had measurable disease at Baseline, and had at least 1 post-baseline response assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>Western Safety Cohort</title>
            <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, once daily (QD) for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 20 cycles. Participants with locally advanced or metastatic solid tumors with no standard therapeutic alternative in the United States were included in this cohort.</description>
          </group>
          <group group_id="O2">
            <title>Pancreatic Cancer Cohort</title>
            <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 4 cycles. Participants with metastatic pancreatic cancer who had progressed after at least 1 line of standard chemotherapy were included in this cohort.</description>
          </group>
          <group group_id="O3">
            <title>Metastatic CRC Cohort</title>
            <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 12 cycles. Participants with metastatic CRC who had progressed after at least 2 lines of previous standard chemotherapy were included in this cohort.</description>
          </group>
          <group group_id="O4">
            <title>sqEC Cohort</title>
            <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 8 cycles. Participants with metastatic sqEC who had progressed after at least 1 line of standard chemotherapy were included in this cohort.</description>
          </group>
          <group group_id="O5">
            <title>sqNSCLC Cohort</title>
            <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 18 cycles. Participants with metastatic sqNSCLC who had progressed after at least 2 lines of standard treatment were included in this cohort.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Response Rate (CR and PR)</title>
          <description>Overall response rate was defined as percentage of participants documented to have unconfirmed CR or PR according to RECIST v1.1 as the best response. CR was defined as disappearance of all lesions, PR was defined as at least a 30% decrease in the sum of the LD of lesions, taking as reference the baseline sum LD.</description>
          <population>Response-evaluable Analysis Set included all participants who received at least 1 dose of study drug, had measurable disease at Baseline, and had at least 1 post-baseline response assessment.</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="12"/>
                <count group_id="O2" value="13"/>
                <count group_id="O3" value="31"/>
                <count group_id="O4" value="19"/>
                <count group_id="O5" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.3" lower_limit="0.90" upper_limit="28.7"/>
                    <measurement group_id="O2" value="0" lower_limit="0" upper_limit="16.2"/>
                    <measurement group_id="O3" value="0" lower_limit="0" upper_limit="7.20"/>
                    <measurement group_id="O4" value="5.3" lower_limit="0.60" upper_limit="19.0"/>
                    <measurement group_id="O5" value="0" lower_limit="0" upper_limit="12.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Response (DOR)</title>
        <description>DOR was defined as the time from the date of first documentation of a CR or PR to the date of first documentation of tumor progression. Per RECIST V1.1, CR was defined as disappearance of all lesions, PR was defined as at least a 30% decrease in the sum of the LD of lesions, taking as reference the baseline sum LD. PD was defined as at least a 20% increase in the sum of the LD of lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.</description>
        <time_frame>From first documented response until disease progression or end of treatment, whichever occurs first (Up to 14 months)</time_frame>
        <population>Response-evaluable Analysis Set included all participants who received at least 1 dose of study drug, had measurable disease at Baseline, and had at least 1 post-baseline response assessment. Only responders were to be analyzed for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Western Safety Cohort</title>
            <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, once daily (QD) for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 20 cycles. Participants with locally advanced or metastatic solid tumors with no standard therapeutic alternative in the United States were included in this cohort.</description>
          </group>
          <group group_id="O2">
            <title>Pancreatic Cancer Cohort</title>
            <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 4 cycles. Participants with metastatic pancreatic cancer who had progressed after at least 1 line of standard chemotherapy were included in this cohort.</description>
          </group>
          <group group_id="O3">
            <title>Metastatic CRC Cohort</title>
            <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 12 cycles. Participants with metastatic CRC who had progressed after at least 2 lines of previous standard chemotherapy were included in this cohort.</description>
          </group>
          <group group_id="O4">
            <title>sqEC Cohort</title>
            <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 8 cycles. Participants with metastatic sqEC who had progressed after at least 1 line of standard chemotherapy were included in this cohort.</description>
          </group>
          <group group_id="O5">
            <title>sqNSCLC Cohort</title>
            <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 18 cycles. Participants with metastatic sqNSCLC who had progressed after at least 2 lines of standard treatment were included in this cohort.</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Response (DOR)</title>
          <description>DOR was defined as the time from the date of first documentation of a CR or PR to the date of first documentation of tumor progression. Per RECIST V1.1, CR was defined as disappearance of all lesions, PR was defined as at least a 30% decrease in the sum of the LD of lesions, taking as reference the baseline sum LD. PD was defined as at least a 20% increase in the sum of the LD of lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.</description>
          <population>Response-evaluable Analysis Set included all participants who received at least 1 dose of study drug, had measurable disease at Baseline, and had at least 1 post-baseline response assessment. Only responders were to be analyzed for this outcome measure.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
                <count group_id="O2" value="0"/>
                <count group_id="O3" value="0"/>
                <count group_id="O4" value="1"/>
                <count group_id="O5" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" lower_limit="NA" upper_limit="NA">Data for median; upper and lower limits of confidence interval (CI) were not available as all responders were censored.</measurement>
                    <measurement group_id="O4" value="NA" lower_limit="NA" upper_limit="NA">Data for median; upper and lower limits of CI were not available as all responders were censored.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression Free Survival (PFS)</title>
        <description>PFS was defined as the time from the date of first dose to the date of first documentation of PD (including clinical progression or clinical deterioration) or death due to any cause, whichever occurs first. Per RECIST V1.1, PD was defined as at least a 20% increase in the sum of the LD of lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.</description>
        <time_frame>From date of randomization until disease progression or death, whichever occurs first (Up to approximately 34 months)</time_frame>
        <population>Safety Analysis Set included all participants who received any amount of study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>Western Safety Cohort</title>
            <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, once daily (QD) for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 20 cycles. Participants with locally advanced or metastatic solid tumors with no standard therapeutic alternative in the United States were included in this cohort.</description>
          </group>
          <group group_id="O2">
            <title>Pancreatic Cancer Cohort</title>
            <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 4 cycles. Participants with metastatic pancreatic cancer who had progressed after at least 1 line of standard chemotherapy were included in this cohort.</description>
          </group>
          <group group_id="O3">
            <title>Metastatic CRC Cohort</title>
            <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 12 cycles. Participants with metastatic CRC who had progressed after at least 2 lines of previous standard chemotherapy were included in this cohort.</description>
          </group>
          <group group_id="O4">
            <title>sqEC Cohort</title>
            <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 8 cycles. Participants with metastatic sqEC who had progressed after at least 1 line of standard chemotherapy were included in this cohort.</description>
          </group>
          <group group_id="O5">
            <title>sqNSCLC Cohort</title>
            <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 18 cycles. Participants with metastatic sqNSCLC who had progressed after at least 2 lines of standard treatment were included in this cohort.</description>
          </group>
        </group_list>
        <measure>
          <title>Progression Free Survival (PFS)</title>
          <description>PFS was defined as the time from the date of first dose to the date of first documentation of PD (including clinical progression or clinical deterioration) or death due to any cause, whichever occurs first. Per RECIST V1.1, PD was defined as at least a 20% increase in the sum of the LD of lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.</description>
          <population>Safety Analysis Set included all participants who received any amount of study drug.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="15"/>
                <count group_id="O3" value="35"/>
                <count group_id="O4" value="21"/>
                <count group_id="O5" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.05" lower_limit="1.31" upper_limit="5.09"/>
                    <measurement group_id="O2" value="1.31" lower_limit="0.99" upper_limit="2.76"/>
                    <measurement group_id="O3" value="1.45" lower_limit="1.35" upper_limit="2.56"/>
                    <measurement group_id="O4" value="3.02" lower_limit="1.25" upper_limit="3.58"/>
                    <measurement group_id="O5" value="2.12" lower_limit="1.28" upper_limit="3.25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival (OS) in the Tumor-Specific Cohorts</title>
        <description>OS was defined as the time from the date of first dose of study drug to death due to any cause.</description>
        <time_frame>Up to approximately 43 months</time_frame>
        <population>Safety Analysis Set included all participants who received any amount of study drug. Participants without documentation of death at the time of analysis were censored at the date last known to be alive. As pre-specified in the protocol, this outcome measure evaluated and reported data for participants only in the Tumor-Specific Cohorts.</population>
        <group_list>
          <group group_id="O1">
            <title>Pancreatic Cancer Cohort</title>
            <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 4 cycles. Participants with metastatic pancreatic cancer who had progressed after at least 1 line of standard chemotherapy were included in this cohort.</description>
          </group>
          <group group_id="O2">
            <title>Metastatic CRC Cohort</title>
            <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 12 cycles. Participants with metastatic CRC who had progressed after at least 2 lines of previous standard chemotherapy were included in this cohort.</description>
          </group>
          <group group_id="O3">
            <title>sqEC Cohort</title>
            <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 8 cycles. Participants with metastatic sqEC who had progressed after at least 1 line of standard chemotherapy were included in this cohort.</description>
          </group>
          <group group_id="O4">
            <title>sqNSCLC Cohort</title>
            <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 18 cycles. Participants with metastatic sqNSCLC who had progressed after at least 2 lines of standard treatment were included in this cohort.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival (OS) in the Tumor-Specific Cohorts</title>
          <description>OS was defined as the time from the date of first dose of study drug to death due to any cause.</description>
          <population>Safety Analysis Set included all participants who received any amount of study drug. Participants without documentation of death at the time of analysis were censored at the date last known to be alive. As pre-specified in the protocol, this outcome measure evaluated and reported data for participants only in the Tumor-Specific Cohorts.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="35"/>
                <count group_id="O3" value="21"/>
                <count group_id="O4" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.67" lower_limit="1.77" upper_limit="7.06"/>
                    <measurement group_id="O2" value="7.72" lower_limit="5.68" upper_limit="11.96"/>
                    <measurement group_id="O3" value="8.61" lower_limit="3.94" upper_limit="42.71"/>
                    <measurement group_id="O4" value="NA" lower_limit="NA" upper_limit="NA">The median, upper and lower limits of 95% confidence interval were not evaluable due to fewer number of participants with events.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Grade &gt;=3 TEAEs, SAEs, TEAEs Leading to Dose Modifications, and TEAEs Leading to Treatment Discontinuation in Tumor-Specific Cohorts</title>
        <description>An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it did not necessarily have to have a causal relationship with this treatment. A TEAE was defined as an adverse event with an onset that occurred after receiving study drug. TEAEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.03, where 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 AE. An SAE was any untoward medical occurrence or effect that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was medically important due to other reasons than the above mentioned criteria.</description>
        <time_frame>From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months)</time_frame>
        <population>Safety Analysis Set included all participants who received any amount of study drug. As pre-specified in the protocol, this outcome measure evaluated and reported data for participants only in the Tumor-Specific Cohorts.</population>
        <group_list>
          <group group_id="O1">
            <title>Pancreatic Cancer Cohort</title>
            <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 4 cycles. Participants with metastatic pancreatic cancer who had progressed after at least 1 line of standard chemotherapy were included in this cohort.</description>
          </group>
          <group group_id="O2">
            <title>Metastatic CRC Cohort</title>
            <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 12 cycles. Participants with metastatic CRC who had progressed after at least 2 lines of previous standard chemotherapy were included in this cohort.</description>
          </group>
          <group group_id="O3">
            <title>sqEC Cohort</title>
            <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 8 cycles. Participants with metastatic sqEC who had progressed after at least 1 line of standard chemotherapy were included in this cohort.</description>
          </group>
          <group group_id="O4">
            <title>sqNSCLC Cohort</title>
            <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 18 cycles. Participants with metastatic sqNSCLC who had progressed after at least 2 lines of standard treatment were included in this cohort.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Grade &gt;=3 TEAEs, SAEs, TEAEs Leading to Dose Modifications, and TEAEs Leading to Treatment Discontinuation in Tumor-Specific Cohorts</title>
          <description>An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it did not necessarily have to have a causal relationship with this treatment. A TEAE was defined as an adverse event with an onset that occurred after receiving study drug. TEAEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.03, where 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 AE. An SAE was any untoward medical occurrence or effect that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was medically important due to other reasons than the above mentioned criteria.</description>
          <population>Safety Analysis Set included all participants who received any amount of study drug. As pre-specified in the protocol, this outcome measure evaluated and reported data for participants only in the Tumor-Specific Cohorts.</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="15"/>
                <count group_id="O2" value="35"/>
                <count group_id="O3" value="21"/>
                <count group_id="O4" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Grade &gt;=3 TEAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="73.3"/>
                    <measurement group_id="O2" value="54.3"/>
                    <measurement group_id="O3" value="57.1"/>
                    <measurement group_id="O4" value="44.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="40.0"/>
                    <measurement group_id="O2" value="22.9"/>
                    <measurement group_id="O3" value="23.8"/>
                    <measurement group_id="O4" value="16.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEAEs Leading to Dose Modifications</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="53.3"/>
                    <measurement group_id="O2" value="48.6"/>
                    <measurement group_id="O3" value="52.4"/>
                    <measurement group_id="O4" value="38.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEAEs Leading to Treatment Discontinuation</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13.3"/>
                    <measurement group_id="O2" value="8.6"/>
                    <measurement group_id="O3" value="9.5"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts</title>
        <description>Clinical laboratory tests included hematology, clinical chemistry and urinalysis. The investigator determined if the results were clinically significant. Only those categories were reported which are clinically significant at post Baseline.</description>
        <time_frame>From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months)</time_frame>
        <population>Safety Analysis Set included all participants who received any amount of study drug. As pre-specified in the protocol, this outcome measure evaluated and reported data for participants only in the Tumor-Specific Cohorts.</population>
        <group_list>
          <group group_id="O1">
            <title>Pancreatic Cancer Cohort</title>
            <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 4 cycles. Participants with metastatic pancreatic cancer who had progressed after at least 1 line of standard chemotherapy were included in this cohort.</description>
          </group>
          <group group_id="O2">
            <title>Metastatic CRC Cohort</title>
            <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 12 cycles. Participants with metastatic CRC who had progressed after at least 2 lines of previous standard chemotherapy were included in this cohort.</description>
          </group>
          <group group_id="O3">
            <title>sqEC Cohort</title>
            <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 8 cycles. Participants with metastatic sqEC who had progressed after at least 1 line of standard chemotherapy were included in this cohort.</description>
          </group>
          <group group_id="O4">
            <title>sqNSCLC Cohort</title>
            <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 18 cycles. Participants with metastatic sqNSCLC who had progressed after at least 2 lines of standard treatment were included in this cohort.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts</title>
          <description>Clinical laboratory tests included hematology, clinical chemistry and urinalysis. The investigator determined if the results were clinically significant. Only those categories were reported which are clinically significant at post Baseline.</description>
          <population>Safety Analysis Set included all participants who received any amount of study drug. As pre-specified in the protocol, this outcome measure evaluated and reported data for participants only in the Tumor-Specific Cohorts.</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="15"/>
                <count group_id="O2" value="35"/>
                <count group_id="O3" value="21"/>
                <count group_id="O4" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Neutrophil Count Decreased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="26.7"/>
                    <measurement group_id="O2" value="17.1"/>
                    <measurement group_id="O3" value="38.1"/>
                    <measurement group_id="O4" value="27.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>White Blood Cell Count Decreased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20.0"/>
                    <measurement group_id="O2" value="8.6"/>
                    <measurement group_id="O3" value="42.9"/>
                    <measurement group_id="O4" value="5.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Lymphocyte Count Decreased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13.3"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="5.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Aspartate Aminotransferase Increased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.7"/>
                    <measurement group_id="O2" value="2.9"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="5.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Alanine Aminotransferase Increased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.7"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="5.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Blood Bilirubin Increased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="2.9"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hepatic Enzyme Increased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.7"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Blood Creatinine Increased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20.0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="4.8"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Blood Creatinine Decreased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.7"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Blood Urea Increased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.7"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Blood Chloride Decreased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.7"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Blood Sodium Decreased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="2.9"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Platelet Count Decreased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="5.7"/>
                    <measurement group_id="O3" value="4.8"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Blood Alkaline Phosphatase Increased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.7"/>
                    <measurement group_id="O2" value="5.7"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Blood Uric Acid Increased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.7"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Blood Glucose Increased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.7"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Blood Albumin Decreased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.7"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Protein Total Decreased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.7"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Haematocrit Decreased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.7"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Red Blood Cell Count Decreased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.7"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Clinically Significant Changes in Vital Sign Measurements, Reported as Adverse Events in Tumor-Specific Cohorts</title>
        <description>Vital signs included assessments of systolic and diastolic blood pressure (BP), heart rate (HR), and body temperature. The investigator determined if the results were clinically significant. Only those categories were reported which are clinically significant at post Baseline.</description>
        <time_frame>From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months)</time_frame>
        <population>Safety Analysis Set included all participants who received any amount of study drug. As pre-specified in the protocol, this outcome measure evaluated and reported data for participants only in the Tumor-Specific Cohorts.</population>
        <group_list>
          <group group_id="O1">
            <title>Pancreatic Cancer Cohort</title>
            <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 4 cycles. Participants with metastatic pancreatic cancer who had progressed after at least 1 line of standard chemotherapy were included in this cohort.</description>
          </group>
          <group group_id="O2">
            <title>Metastatic CRC Cohort</title>
            <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 12 cycles. Participants with metastatic CRC who had progressed after at least 2 lines of previous standard chemotherapy were included in this cohort.</description>
          </group>
          <group group_id="O3">
            <title>sqEC Cohort</title>
            <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 8 cycles. Participants with metastatic sqEC who had progressed after at least 1 line of standard chemotherapy were included in this cohort.</description>
          </group>
          <group group_id="O4">
            <title>sqNSCLC Cohort</title>
            <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 18 cycles. Participants with metastatic sqNSCLC who had progressed after at least 2 lines of standard treatment were included in this cohort.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Clinically Significant Changes in Vital Sign Measurements, Reported as Adverse Events in Tumor-Specific Cohorts</title>
          <description>Vital signs included assessments of systolic and diastolic blood pressure (BP), heart rate (HR), and body temperature. The investigator determined if the results were clinically significant. Only those categories were reported which are clinically significant at post Baseline.</description>
          <population>Safety Analysis Set included all participants who received any amount of study drug. As pre-specified in the protocol, this outcome measure evaluated and reported data for participants only in the Tumor-Specific Cohorts.</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="15"/>
                <count group_id="O2" value="35"/>
                <count group_id="O3" value="21"/>
                <count group_id="O4" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Orthostatic Hypotension</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="2.9"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Tachycardia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="5.7"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Bradycardia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="2.9"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Atrial Fibrillation</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="2.9"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Increase in HR</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="2.9"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months)</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. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.</desc>
      <group_list>
        <group group_id="E1">
          <title>Western Safety Cohort</title>
          <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, once daily (QD) for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 20 cycles. Participants with locally advanced or metastatic solid tumors with no standard therapeutic alternative in the United States were included in this cohort.</description>
        </group>
        <group group_id="E2">
          <title>Pancreatic Cancer Cohort</title>
          <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 4 cycles. Participants with metastatic pancreatic cancer who had progressed after at least 1 line of standard chemotherapy were included in this cohort.</description>
        </group>
        <group group_id="E3">
          <title>Metastatic CRC Cohort</title>
          <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 12 cycles. Participants with metastatic CRC who had progressed after at least 2 lines of previous standard chemotherapy were included in this cohort.</description>
        </group>
        <group group_id="E4">
          <title>sqEC Cohort</title>
          <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 8 cycles. Participants with metastatic sqEC who had progressed after at least 1 line of standard chemotherapy were included in this cohort.</description>
        </group>
        <group group_id="E5">
          <title>sqNSCLC Cohort</title>
          <description>TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 18 cycles. Participants with metastatic sqNSCLC who had progressed after at least 2 lines of standard treatment were included in this cohort.</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="10" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="13" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="17" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="12" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="8" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="8" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="5" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="3" subjects_at_risk="18"/>
              </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="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Upper gastrointestinal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Gastrointestinal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Small intestinal obstruction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Duodenal ulcer perforation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Intestinal obstruction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Large intestine perforation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Disease progression</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Bile duct stenosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Abdominal infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Pyelonephritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </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="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Muscular weakness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Malignant pleural effusion</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Cancer pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Tumour pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Colorectal cancer</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Oesophageal carcinoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Pancreatic carcinoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Pancreatic carcinoma metastatic</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Migraine</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Mental status changes</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </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="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Pneumonia aspiration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Pneumonitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Pulmonary alveolar haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Pulmonary embolism</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</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="5" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="27" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="14" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="14" subjects_at_risk="18"/>
              </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="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="3" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Increased tendency to bruise</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Ear pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Vision blurred</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Vitreous floaters</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="16" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="7" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="7" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="14" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="7" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="4" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Gastrooesophageal reflux disease</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Proctalgia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Abdominal distension</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Ascites</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Faeces discoloured</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Flatulence</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Gingival bleeding</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Rectal discharge</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Rectal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Retching</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Stomatitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Early satiety</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Chest pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="3" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Candida infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Kidney infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Localised infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Skin infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Foot fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Wound</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="6" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="5" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>White blood cell count decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="7" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Ejection fraction decreased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Blood alkaline phosphatase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Blood albumin decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Blood chloride decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Blood creatinine decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Blood creatinine increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Blood glucose increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Blood urea increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Blood uric acid increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Haematocrit decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Hepatic enzyme increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Protein total decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Red blood cell count decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Weight increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="6" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="5" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Hypercalcaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Hyperglycaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Hyperuricaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Iron deficiency</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="18"/>
              </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="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Musculoskeletal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Flank pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Muscular weakness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Musculoskeletal chest pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Cancer pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Malignant pleural effusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Tumour pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Peripheral sensory neuropathy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Tremor</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Neuropathy peripheral</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Dysuria</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Vulvovaginal pruritus</sub_title>
                <description>Number of participants at risk in each arm is based on the female population in this study.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="4" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Haemoptysis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Chronic obstructive pulmonary disease</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Pleuritic pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Productive cough</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Respiratory tract congestion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Upper-airway cough syndrome</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="5" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Dermatitis acneiform</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Dermatitis bullous</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Night sweats</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Photosensitivity reaction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Skin ulcer</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hot flush</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="18"/>
              </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>In general, Investigators may publish clinical data after the earlier of (i) publication by the Sponsor or (ii) 12 months following the abandonment, early termination or database lock; provided a copy of the publication provided to Sponsor at least 30 days ahead of publication, the Sponsor's confidential information is removed as may be requested by Sponsor and Investigator defers publication for up to 60 days in the event Sponsor provides notice that it intends to file a patent application.</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/NCT03261947
org study id: TAK-931-2001
secondary id: U1111-1192-7975
secondary id: JapicCTI-163200
nct id: NCT03261947
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to confirm the safety and tolerability of TAK-931 in a cohort of
      Western participants with metastatic solid tumors and to evaluate the anti-tumor activity of
      TAK-931 in participants with metastatic pancreatic cancer, colorectal cancer (CRC), squamous
      esophageal cancer (sqEC), and squamous non-small-cell lung cancer (sqNSCLC).
Pancreatic Arm Now Closed.

      The drug being tested in this study is called TAK-931. TAK-931 blocks function of a specific
      protein called CDC7 kinase in the human body. TAK-931 is being tested in participants with
      metastatic cancer (colorectal, pancreatic, sqNSCLC and sqEC) in the United States and Japan
      and also in the participants with any type of metastatic cancer with no standard therapeutic
      alternative in the United States only. This study will look at the safety, tolerability and
      pharmacokinetics of TAK-931.

      The study will enroll approximately 160 participants. Participants will be enrolled in 5
      cohorts: 1) Western safety cohort, to be enrolled in the United States only, will include
      non-Japanese participants with metastatic solid tumors and no standard therapeutic
      alternative, 2) Metastatic pancreatic cancer cohort, 3) Metastatic colorectal cancer cohort,
      4) Metastatic sqNSCLC cohort, and 5) Metastatic sqEC cohort. All participants will receive:

      • TAK-931 50 mg (2x25 mg or 5x10 mg) capsules

      All participants will be asked to take one 50 mg (2x25 mg or 5x10 mg) capsule at the same
      time of the day every day for 14 days, followed by 7 days break in 21-day cycles throughout
      the study.

      This multi-center trial will be conducted in the United States and Japan. The overall time to
      participate in this study is approximately 24 months. Participants will make multiple visits
      to the clinic. Participants in both Western cohort and disease specific cohorts will be
      followed for progression-free survival every 12 weeks after the last dose of the study drug
      until the occurrence of disease progression, loss to follow up, consent withdrawal, death,
      start of subsequent antineoplastic therapy, study termination, or until 6 months after
      discontinuation of the study treatment, whichever occurs first. Once disease progression is
      confirmed, participants in the disease-specific cohorts will be followed for overall survival
      every 12 weeks until death, loss to follow up, consent withdrawal, study termination, or
      transfer of a participant to a long term safety study, single participant investigational new
      drug application, or similar program after the last dose of the study drug.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percentage of Participants With Dose Limiting Toxicities (DLTs) in Western Safety Cohort
time frame: Cycle 1 (each cycle = 21 days)
description: DLT:Any following event related to TAK-931 assessed by Common Terminology Criteria for Adverse Events(CTCAE) version4.03;Non-febrile Grade 4 neutropenia; febrile neutropenia: Grade >=3 neutropenia; Grade4 thrombocytopenia; Grade >=3 thrombocytopenia of any duration accompanied by Grade 2 bleeding or requiring transfusion; delay in initiation of Cycle 2 by >14 days due to lack of adequate recovery of treatment-related hematological or nonhematologic toxicities; Grade 2 ejection fraction decreased by echocardiogram(ECHO) or multiple gated acquisition(MUGA) scan; Grade 4 laboratory abnormalities; other Grade 2 nonhematologic toxicities considered by investigator to be related to study drug and dose-limiting; Participants receiving <50% of doses (<7 doses) of planned TAK-931 dosing in Cycle 1 due to study drug-related adverse events(AEs); Grade >=3 nonhematologic toxicity with few exceptions: Grade 3 arthralgia/myalgia, fatigue, laboratory abnormalities, nausea and/or emesis or diarrhea.
measure: Percentage of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), TEAEs Leading to Dose Modifications and TEAEs Leading to Treatment Discontinuation in Western Safety Cohort
time frame: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months)
description: An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A TEAE was defined as an adverse event with an onset that occurred after receiving study drug. An SAE was any untoward medical occurrence or effect that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was medically important due to other reasons than the above mentioned criteria.
measure: Disease Control Rate (DCR) in Tumor-Specific Cohorts
time frame: From first dose up to end of treatment (Up to approximately 14 months)
description: DCR was defined as percentage of participants documented to have unconfirmed CR, PR, or SD for at least 6 weeks from treatment initiation according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) as the best response. CR was defined as disappearance of all lesions. PR was defined as at least a 30% decrease in the sum of the longest diameter (LD) of lesions, taking as reference the baseline sum LD. Stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum LD since the treatment started. PD was defined as at least a 20% increase in the sum of the LD of lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
measure: Cmax: Maximum Observed Plasma Concentration for TAK-931
time frame: Cycle 1 (each cycle = 21 days) Days 1 and 8 pre-dose and at multiple timepoints (up to 24 hours) post-dose
measure: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-931
time frame: Cycle 1 (each cycle = 21 days) Days 1 and 8 pre-dose and at multiple timepoints (up to 24 hours) post-dose
measure: AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for TAK-931
time frame: Cycle 1 (each cycle = 21 days) Days 1 and 8 pre-dose and at multiple timepoints (up to 24 hours) post-dose
measure: AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-931
time frame: Cycle 1 (each cycle = 21 days) Days 1 and 8 pre-dose and at multiple timepoints (up to 24 hours) post-dose
measure: CLr: Renal Clearance of TAK-931
time frame: Cycle 1 (each cycle = 21 days) Day 1 pre-dose and at multiple timepoints (up to 8 hours urine sampling) post-dose
description: CLr is a measure of apparent clearance of the drug from the plasma, renal clearance is a measure of drug excreted through kidneys/urine per unit time.
measure: t1/2z: Terminal Disposition Phase Half-life for TAK-931
time frame: Cycle 1 (each cycle = 21 days) Day 8 pre-dose and at multiple timepoints (up to 24 hours) post-dose
measure: CLss/F: Steady-state Apparent Oral Clearance for TAK-931
time frame: Cycle 1 (each cycle = 21 days) Day 8 pre-dose and at multiple timepoints (up to 24 hours) post-dose
description: CL/F was defined as apparent clearance of the drug from the plasma, calculated as the drug dose divided by AUC.
measure: Rac(AUC): Accumulation Ratio Based on AUC Over the Dosing Interval (AUCτ) for TAK-931
time frame: Cycle 1 (each cycle = 21 days) Day 8 pre-dose and at multiple timepoints (up to 24 hours) post-dose
measure: Overall Response Rate (CR and PR)
time frame: From first dose up to end of treatment (Up to approximately 14 months)
description: Overall response rate was defined as percentage of participants documented to have unconfirmed CR or PR according to RECIST v1.1 as the best response. CR was defined as disappearance of all lesions, PR was defined as at least a 30% decrease in the sum of the LD of lesions, taking as reference the baseline sum LD.
measure: Duration of Response (DOR)
time frame: From first documented response until disease progression or end of treatment, whichever occurs first (Up to 14 months)
description: DOR was defined as the time from the date of first documentation of a CR or PR to the date of first documentation of tumor progression. Per RECIST V1.1, CR was defined as disappearance of all lesions, PR was defined as at least a 30% decrease in the sum of the LD of lesions, taking as reference the baseline sum LD. PD was defined as at least a 20% increase in the sum of the LD of lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
measure: Progression Free Survival (PFS)
time frame: From date of randomization until disease progression or death, whichever occurs first (Up to approximately 34 months)
description: PFS was defined as the time from the date of first dose to the date of first documentation of PD (including clinical progression or clinical deterioration) or death due to any cause, whichever occurs first. Per RECIST V1.1, PD was defined as at least a 20% increase in the sum of the LD of lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
measure: Overall Survival (OS) in the Tumor-Specific Cohorts
time frame: Up to approximately 43 months
description: OS was defined as the time from the date of first dose of study drug to death due to any cause.
measure: Percentage of Participants With Grade >=3 TEAEs, SAEs, TEAEs Leading to Dose Modifications, and TEAEs Leading to Treatment Discontinuation in Tumor-Specific Cohorts
time frame: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months)
description: An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it did not necessarily have to have a causal relationship with this treatment. A TEAE was defined as an adverse event with an onset that occurred after receiving study drug. TEAEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.03, where 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 AE. An SAE was any untoward medical occurrence or effect that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was medically important due to other reasons than the above mentioned criteria.
measure: Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts
time frame: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months)
description: Clinical laboratory tests included hematology, clinical chemistry and urinalysis. The investigator determined if the results were clinically significant. Only those categories were reported which are clinically significant at post Baseline.
measure: Percentage of Participants With Clinically Significant Changes in Vital Sign Measurements, Reported as Adverse Events in Tumor-Specific Cohorts
time frame: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months)
description: Vital signs included assessments of systolic and diastolic blood pressure (BP), heart rate (HR), and body temperature. The investigator determined if the results were clinically significant. Only those categories were reported which are clinically significant at post Baseline.
arm group label: Western Safety Cohort
arm group type: Experimental
description: TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, once daily (QD) for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 20 cycles. Participants with locally advanced or metastatic solid tumors with no standard therapeutic alternative in the United States were included in this cohort.
arm group label: Pancreatic Cancer Cohort
arm group type: Experimental
description: TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 4 cycles. Participants with metastatic pancreatic cancer who had progressed after at least 1 line of standard chemotherapy were included in this cohort.
arm group label: Metastatic CRC Cohort
arm group type: Experimental
description: TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 12 cycles. Participants with metastatic CRC who had progressed after at least 2 lines of previous standard chemotherapy were included in this cohort.
arm group label: sqEC Cohort
arm group type: Experimental
description: TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 8 cycles. Participants with metastatic sqEC who had progressed after at least 1 line of standard chemotherapy were included in this cohort.
arm group label: sqNSCLC Cohort
arm group type: Experimental
description: TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 18 cycles. Participants with metastatic sqNSCLC who had progressed after at least 2 lines of standard treatment were included in this cohort.
intervention type: Drug
intervention name: TAK-931
description: TAK-931 hard gelatin capsules
arm group label: Metastatic CRC Cohort
arm group label: Pancreatic Cancer Cohort
arm group label: Western Safety Cohort
arm group label: sqEC Cohort
arm group label: sqNSCLC Cohort
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: 
facility: 
facility: 
facility: 
facility: 
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facility: 
country: Japan
country: United States
responsible party type: Sponsor
mesh term: Colorectal Neoplasms
mesh term: Pancreatic Neoplasms
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Esophageal Neoplasms
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: 