<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/NCT02259114</url>
  </required_header>
  <id_info>
    <org_study_id>8628-003</org_study_id>
    <secondary_id>OTX015_108</secondary_id>
    <secondary_id>2014-002680-15</secondary_id>
    <secondary_id>MK-8628-003</secondary_id>
    <nct_id>NCT02259114</nct_id>
  </id_info>
  <brief_title>A Dose-Finding Study of Birabresib (MK-8628), a Small Molecule Inhibitor of the Bromodomain and Extra-Terminal (BET) Proteins, in Adults With Selected Advanced Solid Tumors (MK-8628-003)</brief_title>
  <official_title>A Phase IB Trial With OTX015/MK-8628, a Small Molecule Inhibitor of the Bromodomain and Extra-Terminal (BET) Proteins, in Patients With Selected Advanced Solid Tumors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Oncoethix GmbH</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Oncoethix GmbH</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>
      Open-label, phase I, non-randomized, multicentric study of single-agent birabresib (MK-8628)&#xD;
      (formerly known as OTX015) administered according to two distinct regimens to participants&#xD;
      with selected advanced tumors.&#xD;
&#xD;
      The study will be performed in two parts.&#xD;
&#xD;
      Dose Escalation Part:&#xD;
&#xD;
      This step is designed to determine the maximum tolerated dose (MTD) in each of the two&#xD;
      regimens, which will be evaluated in parallel. Participants will receive oral birabresib&#xD;
      according to:&#xD;
&#xD;
      Continuous Dosing Regimen: continuous, once daily for 21 consecutive days (21-day cycles).&#xD;
&#xD;
      OR Days 1-7 Dosing Regimen: once daily on Days 1 to 7, repeated every 3 weeks (21-day cycles;&#xD;
      1 week ON/2 weeks OFF).&#xD;
&#xD;
      Participants will be sequentially assigned to Continuous Dosing Regimen or Days 1-7 Dosing&#xD;
      Regimen according to the next available place and receive birabresib at escalating doses&#xD;
      levels (DL). Cohorts of 3 participants will be treated, and an additional 3 participants will&#xD;
      be treated at the first indication of dose-limiting toxicity (DLT). MTD assessment will be&#xD;
      based on the tolerability observed during the first 21 days of treatment.&#xD;
&#xD;
      Expansion Part:&#xD;
&#xD;
      The efficacy of birabresib in each of the five indications (i.e., Bromodomain-Nuclear Protein&#xD;
      in Testis [BRD-NUT] midline carcinoma, triple negative breast cancer [TNBC], non-small cell&#xD;
      lung cancer [NSCLC] harboring a rearrangement Anaplastic Lymphoma Kinase [ALK] gene/fusion&#xD;
      protein or Kirsten Ras [KRAS] mutation, castrate-resistant prostate cancer, and pancreatic&#xD;
      ductal carcinoma) will be assessed in terms of response (Response Evaluation Criteria in&#xD;
      Solid Tumors v1.1 [RECIST v1.1] or Prostate Cancer Clinical Trials Working Group 2 [PCWG2])&#xD;
      using a selected regimen.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 23, 2014</start_date>
  <completion_date type="Actual">March 3, 2017</completion_date>
  <primary_completion_date type="Actual">March 3, 2017</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) During Cycle 1</measure>
    <time_frame>Up to Cycle 1 Day 21 (Up to 21 days)</time_frame>
    <description>A DLT was defined as any of the following toxicities that were considered by the investigator to be related to MK-8628: Hematologic toxicity: Grade 4 hematologic toxicity or febrile neutropenia, Grade 3 neutropenia with infection, Grade 3 thrombocytopenia with bleeding or lasting &gt;7 days; Non-hematologic toxicity: Grade 3 or 4 non-hematologic toxicity (regardless of duration) unless it was not optimally managed with supportive care, Grade 3 or 4 laboratory abnormality, with or without symptoms, lasting &gt;48 hours, Intolerable Grade 2 non-hematologic toxicity resulting in study drug discontinuation or delay &gt;7 days with or without dose reduction, Designated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) liver test abnormalities; Treatment delay &gt;2 weeks or dose reduction requirement for initiating Cycle 2.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Who Experienced at Least One Adverse Event (AE)</measure>
    <time_frame>Up to approximately 17.5 months (Up to 30 days after last dose of study treatment)</time_frame>
    <description>An AE is defined as any untoward medical occurrence associated with use of study treatment in humans, whether or not considered treatment related. The number of participants who experienced at least one AE is presented.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Who Discontinued Study Treatment Due to an AE</measure>
    <time_frame>Up to approximately 16.5 months</time_frame>
    <description>The number of participants who discontinued study treatment due to an AE is presented.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Best Overall Response as Assessed in Solid Tumors by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) or in Castration-resistant Prostate Cancer (CRPC) by Prostate Cancer Clinical Trials Working Group (PCWG2) Response Criteria</measure>
    <time_frame>Up to approximately 16.5 months</time_frame>
    <description>The best overall response was the best response recorded from the start of the study treatment until the end of treatment. RECIST 1.1 response categories included: Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions; Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions; and Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Observed Maximum Plasma Concentration (Cmax) of MK-8628</measure>
    <time_frame>Cycle 1 Day1: Predose; 0.25, 1, 2, 3 and 7 hours postdose</time_frame>
    <description>Blood samples were obtained at specified time points for pharmacokinetic (PK) analysis of the observed Cmax of MK-8628. The observed Cmax of MK-8628 after administration is presented.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Cmax (Tmax) of MK-8628</measure>
    <time_frame>Cycle 1 Day1: Predose; 0.25, 1, 2, 3 and 7 hours postdose</time_frame>
    <description>Blood samples were obtained at specified time points for PK analysis of the Tmax of MK-8628. The Tmax of MK-8628 after administration is presented.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under to Concentration-Time Curve From 0 to Infinity (AUC0-∞) of MK-8628</measure>
    <time_frame>Cycle 1 Day1: Predose; 0.25, 1, 2, 3 and 7 hours postdose</time_frame>
    <description>Blood samples were obtained at specified time points for PK analysis of the AUC0-∞ of MK-8628. The AUC0-first is AUC0-∞ which is derived from the post-hoc estimate of CL/F from the population model. The AUC0-∞ of MK-8628 after administration is presented.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Volume of Distribution at Steady State (Vdss) of MK-8628</measure>
    <time_frame>Cycle 1 Day1: Predose; 0.25, 1, 2, 3 and 7 hours postdose</time_frame>
    <description>Blood samples were obtained at specified time points for PK analysis of the Vdss of MK-8628. The Vdss of MK-8628 after administration is presented.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal Half-Life (t1/2) of MK-8628</measure>
    <time_frame>Cycle 1 Day1: Predose; 0.25, 1, 2, 3 and 7 hours postdose</time_frame>
    <description>Blood samples were obtained at specified time points for PK analysis of the t1/2 of MK-8628. The t1/2 of MK-8628 after administration is presented.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total Plasma Clearance (CL) of MK-8628</measure>
    <time_frame>Cycle 1 Day1: Predose; 0.25, 1, 2, 3 and 7 hours postdose</time_frame>
    <description>Blood samples were obtained at specified time points for PK analysis of the CL of MK-8628. The CL of MK-8628 after administration is presented.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">47</enrollment>
  <condition>NUT Midline Carcinoma</condition>
  <condition>Triple Negative Breast Cancer</condition>
  <condition>Non-small Cell Lung Cancer With Rearranged ALK Gene/Fusion Protein or KRAS Mutation</condition>
  <condition>Castrate-resistant Prostate Cancer</condition>
  <condition>CRPC</condition>
  <condition>Pancreatic Ductal Adenocarcinoma</condition>
  <arm_group>
    <arm_group_label>Continuous Dosing Regimen</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants receive birabresib capsules once daily in a fasted state in the morning on Days 1-21 of each 21-day cycle. Starting dose for dose escalation is 80 mg.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Days 1-7 Dosing Regimen</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants receive birabresib capsules once daily in a fasted state in the morning on Days 1-7 of each 21-day cycle. Starting dose for dose escalation is 100 mg.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Birabresib</intervention_name>
    <description>Birabresib 10, 20 and/or 40 mg oral capsules</description>
    <arm_group_label>Continuous Dosing Regimen</arm_group_label>
    <arm_group_label>Days 1-7 Dosing Regimen</arm_group_label>
    <other_name>OTX105</other_name>
    <other_name>MK-8628</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Signed informed consent obtained prior to initiation of any study-specific procedures&#xD;
             and treatment;&#xD;
&#xD;
          2. Histologically or cytologically confirmed diagnosis of one of the following advanced&#xD;
             or metastatic solid tumors for which standard therapy either does not exist or has&#xD;
             proven ineffective, intolerable or inacceptable for the patient:&#xD;
&#xD;
               -  NUT midline carcinoma (ectopic expression of NUT protein as determined by&#xD;
                  immunohistochemistry (IHC) and/or detection of BRD-NUT gene translocation as&#xD;
                  determined by fluorescence In situ hybridization [FISH]);&#xD;
&#xD;
               -  Triple negative breast cancer defined according to American Society of Clinical&#xD;
                  Oncology (ASCO) recommendations (Hammond et al., 2010; Wolff et al., 2007);&#xD;
&#xD;
               -  Non-small cell lung cancer harboring a rearranged ALK gene/fusion protein (FISH&#xD;
                  or IHC) or KRAS mutation (as defined by any molecular analysis);&#xD;
&#xD;
               -  Castrate-resistant prostate cancer (CRPC);&#xD;
&#xD;
               -  Pancreatic ductal adenocarcinoma;&#xD;
&#xD;
          3. At least one measurable lesion as per RECIST version 1.1., except for CRPC&#xD;
             participants who may be enrolled with objective evidence of disease as per PCWG2&#xD;
             criteria;&#xD;
&#xD;
          4. Age ≥18 years at the time of informed consent;&#xD;
&#xD;
          5. Life expectancy ≥3 months;&#xD;
&#xD;
          6. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤1;&#xD;
&#xD;
          7. Adequate bone marrow reserve, renal and liver function:&#xD;
&#xD;
               -  Absolute neutrophil count ≥1.5 x10^9/L,&#xD;
&#xD;
               -  Platelet count ≥150 x10^9/L,&#xD;
&#xD;
               -  Hemoglobin ≥9 g/dL,&#xD;
&#xD;
               -  Creatinine clearance ≥30 mL/min calculated according to the Cockroft and Gault&#xD;
                  formula or Modification of Diet in Renal Disease (MDRD) formula for participants&#xD;
                  aged &gt;65 years,&#xD;
&#xD;
               -  Alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≤3 x upper limit&#xD;
                  of normal (ULN) and total bilirubin ≤1.25 x ULN (in case of liver involvement,&#xD;
                  ALT/AST ≤5 x ULN and total bilirubin ≤2 x ULN will be allowed),&#xD;
&#xD;
               -  Serum albumin ≥2.8 g/dL,&#xD;
&#xD;
               -  International Normalized Ratio (INR) ≤1.5 x ULN or INR &lt;3 for participants&#xD;
                  treated with antivitamin K;&#xD;
&#xD;
          8. An interval of ≥3 weeks since chemotherapy (≥6 weeks for nitrosoureas or mitomycin C),&#xD;
             immunotherapy, hormone therapy or any other anticancer therapy or surgical&#xD;
             intervention resection, or ≥3 half-lives for monoclonal antibodies, or ≥5 half-lives&#xD;
             for other non-cytotoxic agents (whichever is longer);&#xD;
&#xD;
          9. CRPC participants must maintain ongoing androgen deprivation therapy with a&#xD;
             gonadotropin releasing hormone (GnRH) analogue, antagonist or orchiectomy providing&#xD;
             serum testosterone is &lt;50 ng/dL (&lt;1.7 nmol/L);&#xD;
&#xD;
         10. Participants receiving bisphosphonate or denosumab therapy must be on stable doses for&#xD;
             at least 4 weeks before initiating study treatment.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Inability to swallow oral medications or presence of a gastrointestinal disorder (e.g.&#xD;
             malabsorption) deemed to jeopardize intestinal absorption of birabresib;&#xD;
&#xD;
          2. Persistent grade &gt;1 clinically significant toxicities related to prior antineoplastic&#xD;
             therapies (except for alopecia); stable sensory neuropathy ≤ grade 2 National Cancer&#xD;
             Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v.4.0 is&#xD;
             accepted.&#xD;
&#xD;
          3. Known primary central nervous system (CNS) malignancy or CNS involvement;&#xD;
&#xD;
          4. History of prior or concomitant malignancies (other than excised non-melanoma skin&#xD;
             cancer or cured in situ cervical carcinoma) within 3 years of study entry;&#xD;
&#xD;
          5. Other serious illness or medical conditions, such as active infection, unresolved&#xD;
             bowel obstruction, or psychiatric disorders;&#xD;
&#xD;
          6. Known human immunodeficiency virus (HIV) positivity;&#xD;
&#xD;
          7. Participation in another clinical trial or treatment with any investigational drug&#xD;
             within 30 days prior to study entry;&#xD;
&#xD;
          8. Other concomitant anticancer treatment;&#xD;
&#xD;
          9. Concomitant therapy with strong CYP3A4 interfering drugs;&#xD;
&#xD;
         10. Current use of anticoagulants (e.g. warfarin, heparin) at therapeutic levels within 7&#xD;
             days prior to the first dose of birabresib. Low-dose (prophylactic) low molecular&#xD;
             weight heparin (LMWH) is permitted;&#xD;
&#xD;
         11. Pregnant or breast-feeding participants, and men and women with childbearing potential&#xD;
             not using effective contraception while on study drug.&#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>Medical Director</last_name>
    <role>Study Director</role>
    <affiliation>Merck Sharp &amp; Dohme LLC</affiliation>
  </overall_official>
  <removed_countries>
    <country>Belgium</country>
    <country>Canada</country>
    <country>France</country>
    <country>Spain</country>
    <country>Switzerland</country>
  </removed_countries>
  <reference>
    <citation>Lewin J, Soria JC, Stathis A, Delord JP, Peters S, Awada A, Aftimos PG, Bekradda M, Rezai K, Zeng Z, Hussain A, Perez S, Siu LL, Massard C. Phase Ib Trial With Birabresib, a Small-Molecule Inhibitor of Bromodomain and Extraterminal Proteins, in Patients With Selected Advanced Solid Tumors. J Clin Oncol. 2018 Oct 20;36(30):3007-3014. doi: 10.1200/JCO.2018.78.2292. Epub 2018 May 7.</citation>
    <PMID>29733771</PMID>
  </reference>
  <verification_date>January 2021</verification_date>
  <study_first_submitted>October 3, 2014</study_first_submitted>
  <study_first_submitted_qc>October 3, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 8, 2014</study_first_posted>
  <results_first_submitted>January 3, 2018</results_first_submitted>
  <results_first_submitted_qc>February 7, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">October 1, 2018</results_first_posted>
  <last_update_submitted>January 7, 2021</last_update_submitted>
  <last_update_submitted_qc>January 7, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">January 26, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Triple Negative Breast Neoplasms</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf</ipd_description>
    <ipd_url>http://engagezone.msd.com/ds_documentation.php</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>November 19, 2015</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/14/NCT02259114/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>February 9, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/14/NCT02259114/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>MK-8628 Continuous Dosing Regimen 80 mg/Day</title>
          <description>Participants received MK-8628 (formerly OTX015) capsules at a total daily dose of 80 mg/day once daily in a fasted state in the morning on Days 1-21 of each 21-day cycle.</description>
        </group>
        <group group_id="P2">
          <title>MK-8628 Continuous Dosing Regimen 100 mg/Day</title>
          <description>Participants received MK-8628 capsules at a total daily dose of 100 mg/day once daily in a fasted state in the morning on Days 1-21 of each 21-day cycle.</description>
        </group>
        <group group_id="P3">
          <title>MK-8628 Days 1-7 Dosing Regimen 100 mg/Day</title>
          <description>Participants received MK-8628 capsules at a total daily dose of 100 mg/day once daily in a fasted state in the morning on Days 1-7 of each 21-day cycle.</description>
        </group>
        <group group_id="P4">
          <title>MK-8628 Days 1-7 Dosing Regimen 120 mg/Day</title>
          <description>Participants received MK-8628 capsules at a total daily dose of 120 mg/day once daily in a fasted state in the morning on Days 1-7 of each 21-day cycle.</description>
        </group>
        <group group_id="P5">
          <title>MK-8628 Days 1-7 Dosing Regimen 160 mg/Day</title>
          <description>Participants received MK-8628 capsules at a total daily dose of 160 mg/day once daily in a fasted state in the morning on Days 1-7 of each 21-day cycle.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="21"/>
                <participants group_id="P2" count="4"/>
                <participants group_id="P3" count="13"/>
                <participants group_id="P4" count="3"/>
                <participants group_id="P5" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Treated</title>
              <participants_list>
                <participants group_id="P1" count="20">One participant was randomized but did not receive treatment due to a protocol violation.</participants>
                <participants group_id="P2" count="4"/>
                <participants group_id="P3" count="13"/>
                <participants group_id="P4" count="3"/>
                <participants group_id="P5" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="21"/>
                <participants group_id="P2" count="4"/>
                <participants group_id="P3" count="13"/>
                <participants group_id="P4" count="3"/>
                <participants group_id="P5" count="6"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Progressive Disease</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="10"/>
                <participants group_id="P4" count="2"/>
                <participants group_id="P5" count="5"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Treatment Delay &gt;2 wks: Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
              </participants_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="1"/>
                <participants group_id="P4" count="1"/>
                <participants group_id="P5" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Treatment Delay &gt;2 wks: Toxicity</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Not Treated</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The Baseline Analysis Population consisted of all participants who received at least one dose of study treatment.</population>
      <group_list>
        <group group_id="B1">
          <title>MK-8628 Continuous Dosing Regimen 80 mg/Day</title>
          <description>Participants received MK-8628 capsules at a total daily dose of 80 mg/day once daily in a fasted state in the morning on Days 1-21 of each 21-day cycle.</description>
        </group>
        <group group_id="B2">
          <title>MK-8628 Continuous Dosing Regimen 100 mg/Day</title>
          <description>Participants received MK-8628 capsules at a total daily dose of 100 mg/day once daily in a fasted state in the morning on Days 1-21 of each 21-day cycle.</description>
        </group>
        <group group_id="B3">
          <title>MK-8628 Days 1-7 Dosing Regimen 100 mg/Day</title>
          <description>Participants received MK-8628 capsules at a total daily dose of 100 mg/day once daily in a fasted state in the morning on Days 1-7 of each 21-day cycle.</description>
        </group>
        <group group_id="B4">
          <title>MK-8628 Days 1-7 Dosing Regimen 120 mg/Day</title>
          <description>Participants received MK-8628 capsules at a total daily dose of 120 mg/day once daily in a fasted state in the morning on Days 1-7 of each 21-day cycle.</description>
        </group>
        <group group_id="B5">
          <title>MK-8628 Days 1-7 Dosing Regimen 160 mg/Day</title>
          <description>Participants received MK-8628 capsules at a total daily dose of 160 mg/day once daily in a fasted state in the morning on Days 1-7 of each 21-day cycle.</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="20"/>
            <count group_id="B2" value="4"/>
            <count group_id="B3" value="13"/>
            <count group_id="B4" value="3"/>
            <count group_id="B5" value="6"/>
            <count group_id="B6" value="46"/>
          </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="20"/>
                    <count group_id="B2" value="4"/>
                    <count group_id="B3" value="13"/>
                    <count group_id="B4" value="3"/>
                    <count group_id="B5" value="6"/>
                    <count group_id="B6" value="46"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="50.2" spread="18.8"/>
                    <measurement group_id="B2" value="62.5" spread="13.5"/>
                    <measurement group_id="B3" value="64.3" spread="9.5"/>
                    <measurement group_id="B4" value="63.3" spread="9.3"/>
                    <measurement group_id="B5" value="58.5" spread="5.3"/>
                    <measurement group_id="B6" value="57.2" spread="15.3"/>
                  </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="20"/>
                    <count group_id="B2" value="4"/>
                    <count group_id="B3" value="13"/>
                    <count group_id="B4" value="3"/>
                    <count group_id="B5" value="6"/>
                    <count group_id="B6" value="46"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="1"/>
                    <measurement group_id="B6" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="13"/>
                    <measurement group_id="B4" value="3"/>
                    <measurement group_id="B5" value="5"/>
                    <measurement group_id="B6" value="39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race and Ethnicity Not Collected</title>
          <population>Race and Ethnicity were not collected from any participant.</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="0"/>
                    <count group_id="B5" value="0"/>
                    <count group_id="B6" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B6" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) During Cycle 1</title>
        <description>A DLT was defined as any of the following toxicities that were considered by the investigator to be related to MK-8628: Hematologic toxicity: Grade 4 hematologic toxicity or febrile neutropenia, Grade 3 neutropenia with infection, Grade 3 thrombocytopenia with bleeding or lasting &gt;7 days; Non-hematologic toxicity: Grade 3 or 4 non-hematologic toxicity (regardless of duration) unless it was not optimally managed with supportive care, Grade 3 or 4 laboratory abnormality, with or without symptoms, lasting &gt;48 hours, Intolerable Grade 2 non-hematologic toxicity resulting in study drug discontinuation or delay &gt;7 days with or without dose reduction, Designated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) liver test abnormalities; Treatment delay &gt;2 weeks or dose reduction requirement for initiating Cycle 2.</description>
        <time_frame>Up to Cycle 1 Day 21 (Up to 21 days)</time_frame>
        <population>The DLT Evaluable Population consisted of all participants who received ≥85% of the planned dose of study treatment (18 days for Continuous Dosing Regimens, or 6 days for Days 1-7 Dosing Regimens) or experienced a DLT during the first 21-day cycle.</population>
        <group_list>
          <group group_id="O1">
            <title>MK-8628 Continuous Dosing Regimen 80 mg/Day</title>
            <description>Participants received MK-8628 capsules at a total daily dose of 80 mg/day once daily in a fasted state in the morning on Days 1-21 of each 21-day cycle.</description>
          </group>
          <group group_id="O2">
            <title>MK-8628 Continuous Dosing Regimen 100 mg/Day</title>
            <description>Participants received MK-8628 capsules at a total daily dose of 100 mg/day once daily in a fasted state in the morning on Days 1-21 of each 21-day cycle.</description>
          </group>
          <group group_id="O3">
            <title>MK-8628 Days 1-7 Dosing Regimen 100 mg/Day</title>
            <description>Participants received MK-8628 capsules at a total daily dose of 100 mg/day once daily in a fasted state in the morning on Days 1-7 of each 21-day cycle.</description>
          </group>
          <group group_id="O4">
            <title>MK-8628 Days 1-7 Dosing Regimen 120 mg/Day</title>
            <description>Participants received MK-8628 capsules at a total daily dose of 120 mg/day once daily in a fasted state in the morning on Days 1-7 of each 21-day cycle.</description>
          </group>
          <group group_id="O5">
            <title>MK-8628 Days 1-7 Dosing Regimen 160 mg/Day</title>
            <description>Participants received MK-8628 capsules at a total daily dose of 160 mg/day once daily in a fasted state in the morning on Days 1-7 of each 21-day cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) During Cycle 1</title>
          <description>A DLT was defined as any of the following toxicities that were considered by the investigator to be related to MK-8628: Hematologic toxicity: Grade 4 hematologic toxicity or febrile neutropenia, Grade 3 neutropenia with infection, Grade 3 thrombocytopenia with bleeding or lasting &gt;7 days; Non-hematologic toxicity: Grade 3 or 4 non-hematologic toxicity (regardless of duration) unless it was not optimally managed with supportive care, Grade 3 or 4 laboratory abnormality, with or without symptoms, lasting &gt;48 hours, Intolerable Grade 2 non-hematologic toxicity resulting in study drug discontinuation or delay &gt;7 days with or without dose reduction, Designated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) liver test abnormalities; Treatment delay &gt;2 weeks or dose reduction requirement for initiating Cycle 2.</description>
          <population>The DLT Evaluable Population consisted of all participants who received ≥85% of the planned dose of study treatment (18 days for Continuous Dosing Regimens, or 6 days for Days 1-7 Dosing Regimens) or experienced a DLT during the first 21-day cycle.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="4"/>
                <count group_id="O3" value="13"/>
                <count group_id="O4" value="3"/>
                <count group_id="O5" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants Who Experienced at Least One Adverse Event (AE)</title>
        <description>An AE is defined as any untoward medical occurrence associated with use of study treatment in humans, whether or not considered treatment related. The number of participants who experienced at least one AE is presented.</description>
        <time_frame>Up to approximately 17.5 months (Up to 30 days after last dose of study treatment)</time_frame>
        <population>The Safety Population consisted of all participants who received at least one dose of study treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>MK-8628 Continuous Dosing Regimen 80 mg/Day</title>
            <description>Participants received MK-8628 capsules at a total daily dose of 80 mg/day once daily in a fasted state in the morning on Days 1-21 of each 21-day cycle.</description>
          </group>
          <group group_id="O2">
            <title>MK-8628 Continuous Dosing Regimen 100 mg/Day</title>
            <description>Participants received MK-8628 capsules at a total daily dose of 100 mg/day once daily in a fasted state in the morning on Days 1-21 of each 21-day cycle.</description>
          </group>
          <group group_id="O3">
            <title>MK-8628 Days 1-7 Dosing Regimen 100 mg/Day</title>
            <description>Participants received MK-8628 capsules at a total daily dose of 100 mg/day once daily in a fasted state in the morning on Days 1-7 of each 21-day cycle.</description>
          </group>
          <group group_id="O4">
            <title>MK-8628 Days 1-7 Dosing Regimen 120 mg/Day</title>
            <description>Participants received MK-8628 capsules at a total daily dose of 120 mg/day once daily in a fasted state in the morning on Days 1-7 of each 21-day cycle.</description>
          </group>
          <group group_id="O5">
            <title>MK-8628 Days 1-7 Dosing Regimen 160 mg/Day</title>
            <description>Participants received MK-8628 capsules at a total daily dose of 160 mg/day once daily in a fasted state in the morning on Days 1-7 of each 21-day cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Who Experienced at Least One Adverse Event (AE)</title>
          <description>An AE is defined as any untoward medical occurrence associated with use of study treatment in humans, whether or not considered treatment related. The number of participants who experienced at least one AE is presented.</description>
          <population>The Safety Population consisted of all participants who received at least one dose of study treatment.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="4"/>
                <count group_id="O3" value="13"/>
                <count group_id="O4" value="3"/>
                <count group_id="O5" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20"/>
                    <measurement group_id="O2" value="4"/>
                    <measurement group_id="O3" value="13"/>
                    <measurement group_id="O4" value="3"/>
                    <measurement group_id="O5" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants Who Discontinued Study Treatment Due to an AE</title>
        <description>The number of participants who discontinued study treatment due to an AE is presented.</description>
        <time_frame>Up to approximately 16.5 months</time_frame>
        <population>The Safety Population consisted of all participants who received at least one dose of study treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>MK-8628 Continuous Dosing Regimen 80 mg/Day</title>
            <description>Participants received MK-8628 capsules at a total daily dose of 80 mg/day once daily in a fasted state in the morning on Days 1-21 of each 21-day cycle.</description>
          </group>
          <group group_id="O2">
            <title>MK-8628 Continuous Dosing Regimen 100 mg/Day</title>
            <description>Participants received MK-8628 capsules at a total daily dose of 100 mg/day once daily in a fasted state in the morning on Days 1-21 of each 21-day cycle.</description>
          </group>
          <group group_id="O3">
            <title>MK-8628 Days 1-7 Dosing Regimen 100 mg/Day</title>
            <description>Participants received MK-8628 capsules at a total daily dose of 100 mg/day once daily in a fasted state in the morning on Days 1-7 of each 21-day cycle.</description>
          </group>
          <group group_id="O4">
            <title>MK-8628 Days 1-7 Dosing Regimen 120 mg/Day</title>
            <description>Participants received MK-8628 capsules at a total daily dose of 120 mg/day once daily in a fasted state in the morning on Days 1-7 of each 21-day cycle.</description>
          </group>
          <group group_id="O5">
            <title>MK-8628 Days 1-7 Dosing Regimen 160 mg/Day</title>
            <description>Participants received MK-8628 capsules at a total daily dose of 160 mg/day once daily in a fasted state in the morning on Days 1-7 of each 21-day cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Who Discontinued Study Treatment Due to an AE</title>
          <description>The number of participants who discontinued study treatment due to an AE is presented.</description>
          <population>The Safety Population consisted of all participants who received at least one dose of study treatment.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="4"/>
                <count group_id="O3" value="13"/>
                <count group_id="O4" value="3"/>
                <count group_id="O5" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="2"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Best Overall Response as Assessed in Solid Tumors by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) or in Castration-resistant Prostate Cancer (CRPC) by Prostate Cancer Clinical Trials Working Group (PCWG2) Response Criteria</title>
        <description>The best overall response was the best response recorded from the start of the study treatment until the end of treatment. RECIST 1.1 response categories included: Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions; Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions; and Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.</description>
        <time_frame>Up to approximately 16.5 months</time_frame>
        <population>The Efficacy Population consisted of all participants who received ≥2 complete cycles (6 weeks) of study treatment and underwent baseline assessment and 1 on-study tumor assessment, or who discontinued early due to disease progression.</population>
        <group_list>
          <group group_id="O1">
            <title>MK-8628 Continuous Dosing Regimen 80 mg/Day</title>
            <description>Participants received MK-8628 capsules at a total daily dose of 80 mg/day once daily in a fasted state in the morning on Days 1-21 of each 21-day cycle.</description>
          </group>
          <group group_id="O2">
            <title>MK-8628 Continuous Dosing Regimen 100 mg/Day</title>
            <description>Participants received MK-8628 capsules at a total daily dose of 100 mg/day once daily in a fasted state in the morning on Days 1-21 of each 21-day cycle.</description>
          </group>
          <group group_id="O3">
            <title>MK-8628 Days 1-7 Dosing Regimen 100 mg/Day</title>
            <description>Participants received MK-8628 capsules at a total daily dose of 100 mg/day once daily in a fasted state in the morning on Days 1-7 of each 21-day cycle.</description>
          </group>
          <group group_id="O4">
            <title>MK-8628 Days 1-7 Dosing Regimen 120 mg/Day</title>
            <description>Participants received MK-8628 capsules at a total daily dose of 120 mg/day once daily in a fasted state in the morning on Days 1-7 of each 21-day cycle.</description>
          </group>
          <group group_id="O5">
            <title>MK-8628 Days 1-7 Dosing Regimen 160 mg/Day</title>
            <description>Participants received MK-8628 capsules at a total daily dose of 160 mg/day once daily in a fasted state in the morning on Days 1-7 of each 21-day cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Best Overall Response as Assessed in Solid Tumors by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) or in Castration-resistant Prostate Cancer (CRPC) by Prostate Cancer Clinical Trials Working Group (PCWG2) Response Criteria</title>
          <description>The best overall response was the best response recorded from the start of the study treatment until the end of treatment. RECIST 1.1 response categories included: Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions; Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions; and Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.</description>
          <population>The Efficacy Population consisted of all participants who received ≥2 complete cycles (6 weeks) of study treatment and underwent baseline assessment and 1 on-study tumor assessment, or who discontinued early due to disease progression.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
                <count group_id="O2" value="2"/>
                <count group_id="O3" value="12"/>
                <count group_id="O4" value="3"/>
                <count group_id="O5" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Complete Response</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Partial Response</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Stable Disease</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="7"/>
                    <measurement group_id="O4" value="1"/>
                    <measurement group_id="O5" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Progressive Disease</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="5"/>
                    <measurement group_id="O4" value="2"/>
                    <measurement group_id="O5" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Not Evaluable</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Observed Maximum Plasma Concentration (Cmax) of MK-8628</title>
        <description>Blood samples were obtained at specified time points for pharmacokinetic (PK) analysis of the observed Cmax of MK-8628. The observed Cmax of MK-8628 after administration is presented.</description>
        <time_frame>Cycle 1 Day1: Predose; 0.25, 1, 2, 3 and 7 hours postdose</time_frame>
        <population>The Pharmacokinetics (PK) Population consisted of all participants who received MK-8628 on Cycle 1 Day 1 and had blood samples drawn for PK analyses.</population>
        <group_list>
          <group group_id="O1">
            <title>MK-8628 Continuous Dosing Regimen 80 mg/Day</title>
            <description>Participants received MK-8628 capsules at a total daily dose of 80 mg/day once daily in a fasted state in the morning on Days 1-21 of each 21-day cycle.</description>
          </group>
          <group group_id="O2">
            <title>MK-8628 Continuous Dosing Regimen 100 mg/Day</title>
            <description>Participants received MK-8628 capsules at a total daily dose of 100 mg/day once daily in a fasted state in the morning on Days 1-21 of each 21-day cycle.</description>
          </group>
          <group group_id="O3">
            <title>MK-8628 Days 1-7 Dosing Regimen 100 mg/Day</title>
            <description>Participants received MK-8628 capsules at a total daily dose of 100 mg/day once daily in a fasted state in the morning on Days 1-7 of each 21-day cycle.</description>
          </group>
          <group group_id="O4">
            <title>MK-8628 Days 1-7 Dosing Regimen 120 mg/Day</title>
            <description>Participants received MK-8628 capsules at a total daily dose of 120 mg/day once daily in a fasted state in the morning on Days 1-7 of each 21-day cycle.</description>
          </group>
          <group group_id="O5">
            <title>MK-8628 Days 1-7 Dosing Regimen 160 mg/Day</title>
            <description>Participants received MK-8628 capsules at a total daily dose of 160 mg/day once daily in a fasted state in the morning on Days 1-7 of each 21-day cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Observed Maximum Plasma Concentration (Cmax) of MK-8628</title>
          <description>Blood samples were obtained at specified time points for pharmacokinetic (PK) analysis of the observed Cmax of MK-8628. The observed Cmax of MK-8628 after administration is presented.</description>
          <population>The Pharmacokinetics (PK) Population consisted of all participants who received MK-8628 on Cycle 1 Day 1 and had blood samples drawn for PK analyses.</population>
          <units>μg/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="4"/>
                <count group_id="O3" value="13"/>
                <count group_id="O4" value="3"/>
                <count group_id="O5" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1466" spread="566"/>
                    <measurement group_id="O2" value="1867" spread="241"/>
                    <measurement group_id="O3" value="1514" spread="377"/>
                    <measurement group_id="O4" value="2052" spread="1130"/>
                    <measurement group_id="O5" value="2670" spread="741"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Cmax (Tmax) of MK-8628</title>
        <description>Blood samples were obtained at specified time points for PK analysis of the Tmax of MK-8628. The Tmax of MK-8628 after administration is presented.</description>
        <time_frame>Cycle 1 Day1: Predose; 0.25, 1, 2, 3 and 7 hours postdose</time_frame>
        <population>The PK Population consisted of all participants who received MK-8628 on Cycle 1 Day 1 and had blood samples drawn for PK analyses.</population>
        <group_list>
          <group group_id="O1">
            <title>MK-8628 Continuous Dosing Regimen 80 mg/Day</title>
            <description>Participants received MK-8628 capsules at a total daily dose of 80 mg/day once daily in a fasted state in the morning on Days 1-21 of each 21-day cycle.</description>
          </group>
          <group group_id="O2">
            <title>MK-8628 Continuous Dosing Regimen 100 mg/Day</title>
            <description>Participants received MK-8628 capsules at a total daily dose of 100 mg/day once daily in a fasted state in the morning on Days 1-21 of each 21-day cycle.</description>
          </group>
          <group group_id="O3">
            <title>MK-8628 Days 1-7 Dosing Regimen 100 mg/Day</title>
            <description>Participants received MK-8628 capsules at a total daily dose of 100 mg/day once daily in a fasted state in the morning on Days 1-7 of each 21-day cycle.</description>
          </group>
          <group group_id="O4">
            <title>MK-8628 Days 1-7 Dosing Regimen 120 mg/Day</title>
            <description>Participants received MK-8628 capsules at a total daily dose of 120 mg/day once daily in a fasted state in the morning on Days 1-7 of each 21-day cycle.</description>
          </group>
          <group group_id="O5">
            <title>MK-8628 Days 1-7 Dosing Regimen 160 mg/Day</title>
            <description>Participants received MK-8628 capsules at a total daily dose of 160 mg/day once daily in a fasted state in the morning on Days 1-7 of each 21-day cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Cmax (Tmax) of MK-8628</title>
          <description>Blood samples were obtained at specified time points for PK analysis of the Tmax of MK-8628. The Tmax of MK-8628 after administration is presented.</description>
          <population>The PK Population consisted of all participants who received MK-8628 on Cycle 1 Day 1 and had blood samples drawn for PK analyses.</population>
          <units>Hours</units>
          <param>Median</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="4"/>
                <count group_id="O3" value="13"/>
                <count group_id="O4" value="3"/>
                <count group_id="O5" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.0" spread="0.6"/>
                    <measurement group_id="O2" value="2.4" spread="0.5"/>
                    <measurement group_id="O3" value="2.9" spread="0.7"/>
                    <measurement group_id="O4" value="1.9" spread="0.6"/>
                    <measurement group_id="O5" value="2.5" spread="0.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Area Under to Concentration-Time Curve From 0 to Infinity (AUC0-∞) of MK-8628</title>
        <description>Blood samples were obtained at specified time points for PK analysis of the AUC0-∞ of MK-8628. The AUC0-first is AUC0-∞ which is derived from the post-hoc estimate of CL/F from the population model. The AUC0-∞ of MK-8628 after administration is presented.</description>
        <time_frame>Cycle 1 Day1: Predose; 0.25, 1, 2, 3 and 7 hours postdose</time_frame>
        <population>The PK Population consisted of all participants who received MK-8628 on Cycle 1 Day 1 and had blood samples drawn for PK analyses.</population>
        <group_list>
          <group group_id="O1">
            <title>MK-8628 Continuous Dosing Regimen 80 mg/Day</title>
            <description>Participants received MK-8628 capsules at a total daily dose of 80 mg/day once daily in a fasted state in the morning on Days 1-21 of each 21-day cycle.</description>
          </group>
          <group group_id="O2">
            <title>MK-8628 Continuous Dosing Regimen 100 mg/Day</title>
            <description>Participants received MK-8628 capsules at a total daily dose of 100 mg/day once daily in a fasted state in the morning on Days 1-21 of each 21-day cycle.</description>
          </group>
          <group group_id="O3">
            <title>MK-8628 Days 1-7 Dosing Regimen 100 mg/Day</title>
            <description>Participants received MK-8628 capsules at a total daily dose of 100 mg/day once daily in a fasted state in the morning on Days 1-7 of each 21-day cycle.</description>
          </group>
          <group group_id="O4">
            <title>MK-8628 Days 1-7 Dosing Regimen 120 mg/Day</title>
            <description>Participants received MK-8628 capsules at a total daily dose of 120 mg/day once daily in a fasted state in the morning on Days 1-7 of each 21-day cycle.</description>
          </group>
          <group group_id="O5">
            <title>MK-8628 Days 1-7 Dosing Regimen 160 mg/Day</title>
            <description>Participants received MK-8628 capsules at a total daily dose of 160 mg/day once daily in a fasted state in the morning on Days 1-7 of each 21-day cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under to Concentration-Time Curve From 0 to Infinity (AUC0-∞) of MK-8628</title>
          <description>Blood samples were obtained at specified time points for PK analysis of the AUC0-∞ of MK-8628. The AUC0-first is AUC0-∞ which is derived from the post-hoc estimate of CL/F from the population model. The AUC0-∞ of MK-8628 after administration is presented.</description>
          <population>The PK Population consisted of all participants who received MK-8628 on Cycle 1 Day 1 and had blood samples drawn for PK analyses.</population>
          <units>μg*h/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="4"/>
                <count group_id="O3" value="13"/>
                <count group_id="O4" value="3"/>
                <count group_id="O5" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12550" spread="4456"/>
                    <measurement group_id="O2" value="19130" spread="6543"/>
                    <measurement group_id="O3" value="12800" spread="3597"/>
                    <measurement group_id="O4" value="16210" spread="9551"/>
                    <measurement group_id="O5" value="27440" spread="10510"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Volume of Distribution at Steady State (Vdss) of MK-8628</title>
        <description>Blood samples were obtained at specified time points for PK analysis of the Vdss of MK-8628. The Vdss of MK-8628 after administration is presented.</description>
        <time_frame>Cycle 1 Day1: Predose; 0.25, 1, 2, 3 and 7 hours postdose</time_frame>
        <population>The PK Population consisted of all participants who received MK-8628 on Cycle 1 Day 1 and had blood samples drawn for PK analyses.</population>
        <group_list>
          <group group_id="O1">
            <title>MK-8628 Continuous Dosing Regimen 80 mg/Day</title>
            <description>Participants received MK-8628 capsules at a total daily dose of 80 mg/day once daily in a fasted state in the morning on Days 1-21 of each 21-day cycle.</description>
          </group>
          <group group_id="O2">
            <title>MK-8628 Continuous Dosing Regimen 100 mg/Day</title>
            <description>Participants received MK-8628 capsules at a total daily dose of 100 mg/day once daily in a fasted state in the morning on Days 1-21 of each 21-day cycle.</description>
          </group>
          <group group_id="O3">
            <title>MK-8628 Days 1-7 Dosing Regimen 100 mg/Day</title>
            <description>Participants received MK-8628 capsules at a total daily dose of 100 mg/day once daily in a fasted state in the morning on Days 1-7 of each 21-day cycle.</description>
          </group>
          <group group_id="O4">
            <title>MK-8628 Days 1-7 Dosing Regimen 120 mg/Day</title>
            <description>Participants received MK-8628 capsules at a total daily dose of 120 mg/day once daily in a fasted state in the morning on Days 1-7 of each 21-day cycle.</description>
          </group>
          <group group_id="O5">
            <title>MK-8628 Days 1-7 Dosing Regimen 160 mg/Day</title>
            <description>Participants received MK-8628 capsules at a total daily dose of 160 mg/day once daily in a fasted state in the morning on Days 1-7 of each 21-day cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Volume of Distribution at Steady State (Vdss) of MK-8628</title>
          <description>Blood samples were obtained at specified time points for PK analysis of the Vdss of MK-8628. The Vdss of MK-8628 after administration is presented.</description>
          <population>The PK Population consisted of all participants who received MK-8628 on Cycle 1 Day 1 and had blood samples drawn for PK analyses.</population>
          <units>Liters</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="4"/>
                <count group_id="O3" value="13"/>
                <count group_id="O4" value="3"/>
                <count group_id="O5" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="44.9" spread="13.4"/>
                    <measurement group_id="O2" value="44.3" spread="5.59"/>
                    <measurement group_id="O3" value="46.9" spread="9.2"/>
                    <measurement group_id="O4" value="44.0" spread="18.3"/>
                    <measurement group_id="O5" value="41.6" spread="15.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Terminal Half-Life (t1/2) of MK-8628</title>
        <description>Blood samples were obtained at specified time points for PK analysis of the t1/2 of MK-8628. The t1/2 of MK-8628 after administration is presented.</description>
        <time_frame>Cycle 1 Day1: Predose; 0.25, 1, 2, 3 and 7 hours postdose</time_frame>
        <population>The PK Population consisted of all participants who received MK-8628 on Cycle 1 Day 1 and had blood samples drawn for PK analyses.</population>
        <group_list>
          <group group_id="O1">
            <title>MK-8628 Continuous Dosing Regimen 80 mg/Day</title>
            <description>Participants received MK-8628 capsules at a total daily dose of 80 mg/day once daily in a fasted state in the morning on Days 1-21 of each 21-day cycle.</description>
          </group>
          <group group_id="O2">
            <title>MK-8628 Continuous Dosing Regimen 100 mg/Day</title>
            <description>Participants received MK-8628 capsules at a total daily dose of 100 mg/day once daily in a fasted state in the morning on Days 1-21 of each 21-day cycle.</description>
          </group>
          <group group_id="O3">
            <title>MK-8628 Days 1-7 Dosing Regimen 100 mg/Day</title>
            <description>Participants received MK-8628 capsules at a total daily dose of 100 mg/day once daily in a fasted state in the morning on Days 1-7 of each 21-day cycle.</description>
          </group>
          <group group_id="O4">
            <title>MK-8628 Days 1-7 Dosing Regimen 120 mg/Day</title>
            <description>Participants received MK-8628 capsules at a total daily dose of 120 mg/day once daily in a fasted state in the morning on Days 1-7 of each 21-day cycle.</description>
          </group>
          <group group_id="O5">
            <title>MK-8628 Days 1-7 Dosing Regimen 160 mg/Day</title>
            <description>Participants received MK-8628 capsules at a total daily dose of 160 mg/day once daily in a fasted state in the morning on Days 1-7 of each 21-day cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Terminal Half-Life (t1/2) of MK-8628</title>
          <description>Blood samples were obtained at specified time points for PK analysis of the t1/2 of MK-8628. The t1/2 of MK-8628 after administration is presented.</description>
          <population>The PK Population consisted of all participants who received MK-8628 on Cycle 1 Day 1 and had blood samples drawn for PK analyses.</population>
          <units>Hours</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="4"/>
                <count group_id="O3" value="13"/>
                <count group_id="O4" value="3"/>
                <count group_id="O5" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.53" spread="0.866"/>
                    <measurement group_id="O2" value="5.93" spread="2.46"/>
                    <measurement group_id="O3" value="3.97" spread="0.46"/>
                    <measurement group_id="O4" value="3.52" spread="0.593"/>
                    <measurement group_id="O5" value="3.99" spread="0.664"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Total Plasma Clearance (CL) of MK-8628</title>
        <description>Blood samples were obtained at specified time points for PK analysis of the CL of MK-8628. The CL of MK-8628 after administration is presented.</description>
        <time_frame>Cycle 1 Day1: Predose; 0.25, 1, 2, 3 and 7 hours postdose</time_frame>
        <population>The PK Population consisted of all participants who received MK-8628 on Cycle 1 Day 1 and had blood samples drawn for PK analyses.</population>
        <group_list>
          <group group_id="O1">
            <title>MK-8628 Continuous Dosing Regimen 80 mg/Day</title>
            <description>Participants received MK-8628 capsules at a total daily dose of 80 mg/day once daily in a fasted state in the morning on Days 1-21 of each 21-day cycle.</description>
          </group>
          <group group_id="O2">
            <title>MK-8628 Continuous Dosing Regimen 100 mg/Day</title>
            <description>Participants received MK-8628 capsules at a total daily dose of 100 mg/day once daily in a fasted state in the morning on Days 1-21 of each 21-day cycle.</description>
          </group>
          <group group_id="O3">
            <title>MK-8628 Days 1-7 Dosing Regimen 100 mg/Day</title>
            <description>Participants received MK-8628 capsules at a total daily dose of 100 mg/day once daily in a fasted state in the morning on Days 1-7 of each 21-day cycle.</description>
          </group>
          <group group_id="O4">
            <title>MK-8628 Days 1-7 Dosing Regimen 120 mg/Day</title>
            <description>Participants received MK-8628 capsules at a total daily dose of 120 mg/day once daily in a fasted state in the morning on Days 1-7 of each 21-day cycle.</description>
          </group>
          <group group_id="O5">
            <title>MK-8628 Days 1-7 Dosing Regimen 160 mg/Day</title>
            <description>Participants received MK-8628 capsules at a total daily dose of 160 mg/day once daily in a fasted state in the morning on Days 1-7 of each 21-day cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Total Plasma Clearance (CL) of MK-8628</title>
          <description>Blood samples were obtained at specified time points for PK analysis of the CL of MK-8628. The CL of MK-8628 after administration is presented.</description>
          <population>The PK Population consisted of all participants who received MK-8628 on Cycle 1 Day 1 and had blood samples drawn for PK analyses.</population>
          <units>Liters/Hour</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="4"/>
                <count group_id="O3" value="13"/>
                <count group_id="O4" value="3"/>
                <count group_id="O5" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.98" spread="1.98"/>
                    <measurement group_id="O2" value="5.69" spread="1.87"/>
                    <measurement group_id="O3" value="8.36" spread="2.16"/>
                    <measurement group_id="O4" value="8.97" spread="4.02"/>
                    <measurement group_id="O5" value="7.39" spread="2.76"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Up to approximately 17.5 months (Up to 30 days after last dose of study treatment)</time_frame>
      <desc>The Safety Population consisted of all participants who received at least one dose of study treatment.</desc>
      <group_list>
        <group group_id="E1">
          <title>MK-8628 Continuous Dosing Regimen 80 mg/Day</title>
          <description>Participants received MK-8628 capsules at a total daily dose of 80 mg/day once daily in a fasted state in the morning on Days 1-21 of each 21-day cycle.</description>
        </group>
        <group group_id="E2">
          <title>MK-8628 Continuous Dosing Regimen 100 mg/Day</title>
          <description>Participants received MK-8628 capsules at a total daily dose of 100 mg/day once daily in a fasted state in the morning on Days 1-21 of each 21-day cycle.</description>
        </group>
        <group group_id="E3">
          <title>MK-8628 Days 1-7 Dosing Regimen 100 mg/Day</title>
          <description>Participants received MK-8628 capsules at a total daily dose of 100 mg/day once daily in a fasted state in the morning on Days 1-7 of each 21-day cycle.</description>
        </group>
        <group group_id="E4">
          <title>MK-8628 Days 1-7 Dosing Regimen 120 mg/Day</title>
          <description>Participants received MK-8628 capsules at a total daily dose of 120 mg/day once daily in a fasted state in the morning on Days 1-7 of each 21-day cycle.</description>
        </group>
        <group group_id="E5">
          <title>MK-8628 Days 1-7 Dosing Regimen 160 mg/Day</title>
          <description>Participants received MK-8628 capsules at a total daily dose of 160 mg/day once daily in a fasted state in the morning on Days 1-7 of each 21-day cycle.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 20.0</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="3" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="4"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="4"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="13"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Disseminated intravascular coagulation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E2" events="7" subjects_affected="2" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Cardiac arrest</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Pericardial effusion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>General physical health deterioration</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" events="5" subjects_affected="2" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperbilirubinaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Appendicitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Skin infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Spinal cord infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Skull fracture</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="20"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E4" events="2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </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" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Bone pain</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Cerebral haemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Cerebral ischaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Peripheral motor neuropathy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Spinal cord compression</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </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" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Urinary tract obstruction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Pneumomediastinum</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Respiratory failure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Embolism</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 20.0</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="20" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="4"/>
                <counts group_id="E3" subjects_affected="13" subjects_at_risk="13"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="6" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" events="19" subjects_affected="7" subjects_at_risk="20"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="4"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="13"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" events="3" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" events="10" subjects_affected="4" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Congenital, familial and genetic disorders</title>
            <event_list>
              <event>
                <sub_title>Factor VII deficiency</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Vision blurred</sub_title>
                <counts group_id="E1" events="5" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Visual acuity reduced</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Visual impairment</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="10" subjects_affected="7" subjects_at_risk="20"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="13"/>
                <counts group_id="E4" events="3" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E5" events="4" subjects_affected="4" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="20"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E3" events="14" subjects_affected="7" subjects_at_risk="13"/>
                <counts group_id="E4" events="5" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E5" events="17" subjects_affected="6" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="15" subjects_affected="9" subjects_at_risk="20"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E3" events="6" subjects_affected="5" subjects_at_risk="13"/>
                <counts group_id="E4" events="10" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E5" events="10" subjects_affected="5" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Stomatitis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="12" subjects_affected="5" subjects_at_risk="20"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E3" events="9" subjects_affected="6" subjects_at_risk="13"/>
                <counts group_id="E4" events="3" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E5" events="8" subjects_affected="3" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" events="14" subjects_affected="10" subjects_at_risk="20"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="4"/>
                <counts group_id="E3" events="8" subjects_affected="6" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="12" subjects_affected="3" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Chest pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Crying</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="6" subjects_affected="3" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="3" subjects_affected="2" subjects_at_risk="13"/>
                <counts group_id="E4" events="12" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E5" events="4" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>General physical health deterioration</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Localised oedema</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Mucosal inflammation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="3" subjects_affected="2" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Hepatotoxicity</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Folliculitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Genital herpes</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Herpes zoster</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Mucosal infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Oral herpes</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Spinal cord infection</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Subdural haemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="4" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Blood creatinine increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Coagulation factor VII level increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" events="27" subjects_affected="5" subjects_at_risk="20"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" events="9" subjects_affected="7" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="3" subjects_affected="2" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" events="13" subjects_affected="8" subjects_at_risk="20"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E3" events="5" subjects_affected="4" subjects_at_risk="13"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E5" events="12" subjects_affected="5" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hyperglycaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hypomagnesaemia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hypophosphataemia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E4" events="2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Arthritis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="6" subjects_affected="5" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="3" subjects_affected="2" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Bone pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="8" subjects_affected="3" subjects_at_risk="13"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Muscular weakness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Musculoskeletal pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" events="6" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Paraesthesia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Sciatica</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Tremor</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Confusional state</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </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" events="2" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Dysuria</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Dysphonia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" events="10" subjects_affected="8" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="5" subjects_affected="4" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Pleuritic pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hyperhidrosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="3" subjects_affected="2" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hot flush</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </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>Subject to obligations of confidentiality, the investigator reserves the right to publish only the results of the work performed pursuant to this protocol, provided, however, that the investigator provides an authorized representative of the Sponsor with a copy of any proposed publication for review and comment at least 45 days in advance of its submission for publication.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Senior Vice President, Global Clinical Development</name_or_title>
      <organization>Merck Sharp &amp; Dohme Corp.</organization>
      <phone>1-800-672-6372</phone>
      <email>ClinicalTrialsDisclosure@merck.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/NCT02259114
org study id: 8628-003
secondary id: OTX015_108
secondary id: 2014-002680-15
secondary id: MK-8628-003
nct id: NCT02259114
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
Open-label, phase I, non-randomized, multicentric study of single-agent birabresib (MK-8628)
      (formerly known as OTX015) administered according to two distinct regimens to participants
      with selected advanced tumors.

      The study will be performed in two parts.

      Dose Escalation Part:

      This step is designed to determine the maximum tolerated dose (MTD) in each of the two
      regimens, which will be evaluated in parallel. Participants will receive oral birabresib
      according to:

      Continuous Dosing Regimen: continuous, once daily for 21 consecutive days (21-day cycles).

      OR Days 1-7 Dosing Regimen: once daily on Days 1 to 7, repeated every 3 weeks (21-day cycles;
      1 week ON/2 weeks OFF).

      Participants will be sequentially assigned to Continuous Dosing Regimen or Days 1-7 Dosing
      Regimen according to the next available place and receive birabresib at escalating doses
      levels (DL). Cohorts of 3 participants will be treated, and an additional 3 participants will
      be treated at the first indication of dose-limiting toxicity (DLT). MTD assessment will be
      based on the tolerability observed during the first 21 days of treatment.

      Expansion Part:

      The efficacy of birabresib in each of the five indications (i.e., Bromodomain-Nuclear Protein
      in Testis [BRD-NUT] midline carcinoma, triple negative breast cancer [TNBC], non-small cell
      lung cancer [NSCLC] harboring a rearrangement Anaplastic Lymphoma Kinase [ALK] gene/fusion
      protein or Kirsten Ras [KRAS] mutation, castrate-resistant prostate cancer, and pancreatic
      ductal carcinoma) will be assessed in terms of response (Response Evaluation Criteria in
      Solid Tumors v1.1 [RECIST v1.1] or Prostate Cancer Clinical Trials Working Group 2 [PCWG2])
      using a selected regimen.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) During Cycle 1
time frame: Up to Cycle 1 Day 21 (Up to 21 days)
description: A DLT was defined as any of the following toxicities that were considered by the investigator to be related to MK-8628: Hematologic toxicity: Grade 4 hematologic toxicity or febrile neutropenia, Grade 3 neutropenia with infection, Grade 3 thrombocytopenia with bleeding or lasting >7 days; Non-hematologic toxicity: Grade 3 or 4 non-hematologic toxicity (regardless of duration) unless it was not optimally managed with supportive care, Grade 3 or 4 laboratory abnormality, with or without symptoms, lasting >48 hours, Intolerable Grade 2 non-hematologic toxicity resulting in study drug discontinuation or delay >7 days with or without dose reduction, Designated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) liver test abnormalities; Treatment delay >2 weeks or dose reduction requirement for initiating Cycle 2.
measure: Number of Participants Who Experienced at Least One Adverse Event (AE)
time frame: Up to approximately 17.5 months (Up to 30 days after last dose of study treatment)
description: An AE is defined as any untoward medical occurrence associated with use of study treatment in humans, whether or not considered treatment related. The number of participants who experienced at least one AE is presented.
measure: Number of Participants Who Discontinued Study Treatment Due to an AE
time frame: Up to approximately 16.5 months
description: The number of participants who discontinued study treatment due to an AE is presented.
measure: Best Overall Response as Assessed in Solid Tumors by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) or in Castration-resistant Prostate Cancer (CRPC) by Prostate Cancer Clinical Trials Working Group (PCWG2) Response Criteria
time frame: Up to approximately 16.5 months
description: The best overall response was the best response recorded from the start of the study treatment until the end of treatment. RECIST 1.1 response categories included: Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions; Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions; and Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
measure: Observed Maximum Plasma Concentration (Cmax) of MK-8628
time frame: Cycle 1 Day1: Predose; 0.25, 1, 2, 3 and 7 hours postdose
description: Blood samples were obtained at specified time points for pharmacokinetic (PK) analysis of the observed Cmax of MK-8628. The observed Cmax of MK-8628 after administration is presented.
measure: Time to Cmax (Tmax) of MK-8628
time frame: Cycle 1 Day1: Predose; 0.25, 1, 2, 3 and 7 hours postdose
description: Blood samples were obtained at specified time points for PK analysis of the Tmax of MK-8628. The Tmax of MK-8628 after administration is presented.
measure: Area Under to Concentration-Time Curve From 0 to Infinity (AUC0-∞) of MK-8628
time frame: Cycle 1 Day1: Predose; 0.25, 1, 2, 3 and 7 hours postdose
description: Blood samples were obtained at specified time points for PK analysis of the AUC0-∞ of MK-8628. The AUC0-first is AUC0-∞ which is derived from the post-hoc estimate of CL/F from the population model. The AUC0-∞ of MK-8628 after administration is presented.
measure: Volume of Distribution at Steady State (Vdss) of MK-8628
time frame: Cycle 1 Day1: Predose; 0.25, 1, 2, 3 and 7 hours postdose
description: Blood samples were obtained at specified time points for PK analysis of the Vdss of MK-8628. The Vdss of MK-8628 after administration is presented.
measure: Terminal Half-Life (t1/2) of MK-8628
time frame: Cycle 1 Day1: Predose; 0.25, 1, 2, 3 and 7 hours postdose
description: Blood samples were obtained at specified time points for PK analysis of the t1/2 of MK-8628. The t1/2 of MK-8628 after administration is presented.
measure: Total Plasma Clearance (CL) of MK-8628
time frame: Cycle 1 Day1: Predose; 0.25, 1, 2, 3 and 7 hours postdose
description: Blood samples were obtained at specified time points for PK analysis of the CL of MK-8628. The CL of MK-8628 after administration is presented.
arm group label: Continuous Dosing Regimen
arm group type: Experimental
description: Participants receive birabresib capsules once daily in a fasted state in the morning on Days 1-21 of each 21-day cycle. Starting dose for dose escalation is 80 mg.
arm group label: Days 1-7 Dosing Regimen
arm group type: Experimental
description: Participants receive birabresib capsules once daily in a fasted state in the morning on Days 1-7 of each 21-day cycle. Starting dose for dose escalation is 100 mg.
intervention type: Drug
intervention name: Birabresib
description: Birabresib 10, 20 and/or 40 mg oral capsules
arm group label: Continuous Dosing Regimen
arm group label: Days 1-7 Dosing Regimen
other name: OTX105
other name: MK-8628
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Medical Director
role: Study Director
affiliation: Merck Sharp & Dohme LLC
country: Belgium
country: Canada
country: France
country: Spain
country: Switzerland
citation: Lewin J, Soria JC, Stathis A, Delord JP, Peters S, Awada A, Aftimos PG, Bekradda M, Rezai K, Zeng Z, Hussain A, Perez S, Siu LL, Massard C. Phase Ib Trial With Birabresib, a Small-Molecule Inhibitor of Bromodomain and Extraterminal Proteins, in Patients With Selected Advanced Solid Tumors. J Clin Oncol. 2018 Oct 20;36(30):3007-3014. doi: 10.1200/JCO.2018.78.2292. Epub 2018 May 7.
PMID: 29733771
responsible party type: Sponsor
mesh term: Triple Negative Breast Neoplasms
sharing ipd: Yes
ipd description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
ipd url: http://engagezone.msd.com/ds_documentation.php
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 