<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/NCT02203513</url>
  </required_header>
  <id_info>
    <org_study_id>140156</org_study_id>
    <secondary_id>14-C-0156</secondary_id>
    <nct_id>NCT02203513</nct_id>
  </id_info>
  <brief_title>A Phase II Single Arm Pilot Study of the Chk1/2 Inhibitor (LY2606368) in BRCA1/2 Mutation Associated Breast or Ovarian Cancer, Triple Negative Breast Cancer, High Grade Serous Ovarian Cancer, and Metastatic Castrate-Resistant Prostate Cancer</brief_title>
  <official_title>A Phase II Single Arm Pilot Study of the Chk1/2 Inhibitor (LY2606368) In BRCA1/2 Mutation Associated Breast or Ovarian Cancer, Triple Negative Breast Cancer, and High Grade Serous Ovarian Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Institutes of Health Clinical Center (CC)</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>
      Background:&#xD;
&#xD;
        -  All cells go through cycles which allow them to divide. In normal cells, checkpoint&#xD;
           kinase 1 (Chk1) and checkpoint kinase 2 (Chk2) (CHEK 2 (Chk1/2) stop cell division at&#xD;
           various points to allow any damage to deoxyribonucleic acid (DNA) to be repaired.&#xD;
&#xD;
        -  When Chk1/2 are not present, cells stop dividing and eventually die. Chk1/2 Inhibitor&#xD;
           (Prexasertib (LY2606368) blocks the Chk1/2 proteins.&#xD;
&#xD;
        -  Researchers hope that by blocking Chk1/2, it will cause tumor cells to die, thereby&#xD;
           shrinking tumors.&#xD;
&#xD;
      Objective:&#xD;
&#xD;
      - To see if LY2606368 helps shrink tumors in patients with certain breast, ovarian or&#xD;
      prostate cancers.&#xD;
&#xD;
      Eligibility:&#xD;
&#xD;
      - Participants at least 18 years old with breast or ovarian cancer. They must have a mutation&#xD;
      in BRCA1 BReast CAncer gene 1 and BRCA2 BReast CAncer gene 2 (BRCA1/2) genes for group 1,&#xD;
      high grade serious ovarian cancer without BRCA1/2 mutation for group 2, or triple negative&#xD;
      breast cancer without BRCA1/2 mutation for group 3, or prostate cancer with or without&#xD;
      BRCA1/2 mutation for group 4.&#xD;
&#xD;
      Design:&#xD;
&#xD;
        -  Participants will be screened with a medical history and physical exam. They will have&#xD;
           blood tests, an electrocardiogram (ECG) heart test, scans, and X-rays. They will have a&#xD;
           piece of their tumor removed at entry (computed tomography (CT)-assisted biopsy).&#xD;
&#xD;
        -  Study Day 1: Participants will have a physical exam and blood drawn. They may have a CT&#xD;
           scan of the chest, abdomen, and pelvis.&#xD;
&#xD;
        -  Day 1 and Day 15 of each 28-day cycle: Participants will receive the study drug through&#xD;
           an intravenous (IV).&#xD;
&#xD;
        -  Vital signs will be checked before and after. An ECG will be done within 1 hour after.&#xD;
&#xD;
        -  Day 15 and Day 28: Participants will have a physical exam, blood drawn, and a 12 lead&#xD;
           ECG.&#xD;
&#xD;
        -  Cycle 1: Participants will have weekly phone calls and blood draws. Participants may&#xD;
           have another CT-assisted biopsy at the end of cycle 1.&#xD;
&#xD;
        -  Cycle 2 and beyond, blood will be drawn every other week for routine blood tests.&#xD;
&#xD;
        -  Participants will have an after-study visit with a physical exam and blood tests.&#xD;
           Participants may have another biopsy when they progressed on treatment. They will have&#xD;
           scans of the chest, pelvis, and abdomen and a 12 lead ECG.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background:&#xD;
&#xD;
        -  Checkpoint kinases 1 and 2 (Chk1/2) are major regulators of the cell cycle and are&#xD;
           intimately associated with the cellular response to deoxyribonucleic acid (DNA) damage&#xD;
           and repair. Chk1/2 also function as the primary mediators of cell cycle arrest in tumors&#xD;
           with tumor protein P53 (p53) dysfunction, such as high-grade serous ovarian cancer&#xD;
           (HGSOC), and triple negative breast cancer (TNBC).&#xD;
&#xD;
        -  Participants with germline BRCA1 BReast CAncer gene 1 and BRCA2 BReast CAncer gene 2&#xD;
           (BRCA1/2) mutation have inherent defects in DNA damage repair pathways.&#xD;
&#xD;
        -  Chk1/2 inhibition alone yielded DNA damage and mitotic catastrophe preclinically, even&#xD;
           in the absence of DNA damage by external agents in tumors with underlying DNA repair&#xD;
           dysfunction.&#xD;
&#xD;
        -  The second-generation Chk1/2 inhibitor (Prexasertib (LY2606368) yielded safety and&#xD;
           preliminary single agent activity in advanced cancer participants.&#xD;
&#xD;
        -  We hypothesize that LY2606368 will result in clinical benefit in participants with&#xD;
           Germline BRCA-Mutated (gBRCAm)-associated breast or ovarian cancers, and HGSOC and TNBC&#xD;
           with low genetic risk.&#xD;
&#xD;
      Objectives:&#xD;
&#xD;
        -  To determine the objective response rate (Complete Response (CR)+Partial Response (PR)&#xD;
           of single agent LY2606368 in patients with gBRCAm-associated breast or ovarian cancer,&#xD;
           HGSOC and TNBC with low genetic risk.&#xD;
&#xD;
        -  To determine the safety and toxicity, and progression-free interval (PFI) of LY2606368&#xD;
           in pretreated participants.&#xD;
&#xD;
        -  To determine biochemical changes in the DNA damage repair and cell cycle check point&#xD;
           pathways in tumor and blood samples in response to treatment.&#xD;
&#xD;
        -  To determine potential resistance mechanisms to LY2606368 treatment in HGSOC.&#xD;
&#xD;
      Eligibility:&#xD;
&#xD;
        -  Participants with recurrent/refractory BReast CAncer gene (BRCA) mutant breast or&#xD;
           ovarian cancer, HGSOC, and TNBC, for whom there remains no standard curative measures.&#xD;
&#xD;
        -  A documented deleterious germline or somatic BRCA mutation for breast or ovarian cancer&#xD;
           participants enrolling in Cohort 1.&#xD;
&#xD;
        -  Negative BRCA mutation testing or negative family history of hereditary breast and&#xD;
           ovarian cancer syndrome for HGSOC (Cohort 2).&#xD;
&#xD;
        -  Negative BRCA mutation testing or negative family history of hereditary breast and&#xD;
           ovarian cancer syndrome for TNBC (Cohort 3).&#xD;
&#xD;
        -  Effective with amendment I (version date 4/24/2017), Metastatic Castration-Resistant&#xD;
           Prostate Cancer (mCRPC), Cohort 4 was closed.&#xD;
&#xD;
        -  Negative BRCA mutation testing or negative family history of hereditary breast and&#xD;
           ovarian cancer syndrome for recurrent platinum-resistant HGSOC with measurable and&#xD;
           biopsiable disease (Cohort 5).&#xD;
&#xD;
        -  Negative BRCA mutation testing or negative family history of hereditary breast and&#xD;
           ovarian cancer syndrome for recurrent platinum-resistant HGSOC with measurable but&#xD;
           without biopsiable disease (Cohort 6).&#xD;
&#xD;
        -  Participants must be off prior chemotherapy, radiation therapy, hormonal therapy, or&#xD;
           biological therapy for at least 4 weeks.&#xD;
&#xD;
        -  Eastern Cooperative Oncology Group (ECOG) performance status 0-2 and adequate organ and&#xD;
           marrow function.&#xD;
&#xD;
      Design:&#xD;
&#xD;
        -  This is an open label, single arm phase II trial to examine activity of LY2606368 in&#xD;
           participants in the 6 independent cohorts (Cohorts 1-6).&#xD;
&#xD;
        -  LY2606368 will be dosed at the recommended phase 2 dose (RP2D) of 105 mg/m^2 intravenous&#xD;
           (IV) once every 14 days of a 28 day-cycle.&#xD;
&#xD;
        -  Research samples including whole blood, circulating tumor cells (CTCs), and tumor&#xD;
           biopsies will be obtained for pharmacodynamics (PD) endpoints at baseline, Cycle 1 Day&#xD;
           15 (6-24hour (hr) post-2nd dose), and/or at progression in all participants. Tumor&#xD;
           biopsies will not be performed in Cohort 6.&#xD;
&#xD;
        -  Participants (Cohorts 1-3, 5 and 6) will be evaluated every two cycles for response&#xD;
           using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and every cycle for&#xD;
           safety using Common Terminology Criteria for Adverse Events (CTCAE) v4.0.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Eli Lilly prematurely terminated the study.&#xD;
  </why_stopped>
  <start_date type="Actual">January 20, 2015</start_date>
  <completion_date type="Actual">August 27, 2021</completion_date>
  <primary_completion_date type="Actual">August 27, 2021</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Objective Response (Complete Response (CR) + Partial Response (PR)</measure>
    <time_frame>Cohorts 1-3, 5, &amp; 6 were restaged every 2 mos. Cohort 4 was restaged every 3 mos. Restaging continued until participant's disease was deemed progressive by RECIST or until removed from treatment for other etiology for an combined average of 133 days.</time_frame>
    <description>Objective response (CR+PR) of single agent Prexasertib (LY2606368) in participants with germline BReast CAncer gene -Mutated (gBRCAm)-associated breast and ovarian cancers, high grade serous ovarian cancer (HGSOC) and triple-negative breast cancer (TNBC) at low genetic risk. Response was measured using the Response Evaluation Criteria in Solid Tumors (RECIST)v1.1. Complete Response is disappearance of all target lesions. Partial Response is at least a 30% decrease in the sum of diameters of target lesions.</description>
  </primary_outcome>
  <other_outcome>
    <measure>Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0).</measure>
    <time_frame>Participants were followed for the duration of treatment and up to 4 weeks after being off treatment, an average of 7 months</time_frame>
    <description>Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">111</enrollment>
  <condition>Ovarian Cancer</condition>
  <condition>Breast Cancer</condition>
  <condition>Prostate Cancer</condition>
  <arm_group>
    <arm_group_label>Arm 1-Prexasertib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Prexasertib (LY2606368) monotherapy treatment</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>LY2606368</intervention_name>
    <description>105 mg/m^2 intravenous (IV) once every 14 days of a 28 day cycle</description>
    <arm_group_label>Arm 1-Prexasertib</arm_group_label>
    <other_name>Prexasertib</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        -  INCLUSION CRITERIA:&#xD;
&#xD;
               1. A documented deleterious germline breast cancer 1 and breast cancer 2 mutation&#xD;
                  (gBRCA1/2m) obtained in a Clinical Laboratory Improvement Amendments&#xD;
                  (CLIA)-certified laboratory, including but not limited to Myriad Genetics, either&#xD;
                  by multi-gene panels or individual testing, for Cohort 1 participants prior to&#xD;
                  study enrollment. Participants with documented somatic BReast CAncer gene (BRCA)&#xD;
                  mutation obtained in a CLIA-certified laboratory also will be considered for&#xD;
                  Cohort 1. Variants of uncertain significance (VUS) of BRCA1/2 are not considered&#xD;
                  deleterious. Participants with variant of uncertain significance (VUS) or&#xD;
                  deleterious mutation in other genes without gBRCA1/2m can be considered for&#xD;
                  Cohort 2 or 3 or 5.&#xD;
&#xD;
               2. Participants enrolling in the sporadic high grade serous epithelial or high grade&#xD;
                  endometrioid ovarian cancer group, Cohort 2, must have a negative family history&#xD;
                  of hereditary breast ovarian cancer (HBOC) syndrome, or negative gBRCA1/2m&#xD;
                  mutation test.&#xD;
&#xD;
               3. Participants enrolling in the triple negative breast cancer (estrogen receptor&#xD;
                  (ER)-/progesterone receptor (PR)-/human epidermal growth factor receptor 2&#xD;
                  (Her2)-) group, Cohort 3, must have a negative family history of HBOC syndrome,&#xD;
                  or negative gBRCA1/2m test. A family history of HBOC is defined by National&#xD;
                  Comprehensive Cancer Network® (NCCN®) Genetic/Familial High-Risk Assessment:&#xD;
                  Breast and Ovarian guideline.&#xD;
&#xD;
               4. For Cohorts 1-3, 5 and 6: participants must have breast and/or epithelial or&#xD;
                  endometrioid ovarian cancer, primary peritoneal cancer, and/or fallopian tube&#xD;
                  cancer histologically or cytologically confirmed at the National Cancer Institute&#xD;
                  (NCI) that is metastatic or unresectable and for which standard curative measures&#xD;
                  do not exist or are no longer effective. ER/PR/HER2 status needs to be documented&#xD;
                  either by an outside source or at NCI. Participants with gBRCA1/2m with history&#xD;
                  of or active breast and ovarian cancers are considered for Cohort 1.&#xD;
&#xD;
                  Participants enrolling in Cohort 5, the recurrent platinum-resistant sporadic&#xD;
                  high grade serous epithelial or high grade endometrioid ovarian cancer group,&#xD;
                  must have a negative family history of HBOC syndrome, or negative gBRCA1/2m test.&#xD;
                  Participants should have recurrent platinum-resistant - defined as disease&#xD;
                  recurrence by imaging within 6 months of the last receipt of platinum-based&#xD;
                  chemotherapy. Rising mucin 16 (CA125) only is not considered as&#xD;
                  platinum-resistant disease. Participants with primary platinum refractory disease&#xD;
                  defined as progression during or within 3 months after receiving first-line&#xD;
                  platinum-based chemotherapy are not eligible.&#xD;
&#xD;
               5. All participants must have measurable disease, defined as at least one lesion&#xD;
                  that can be accurately measured in at least one dimension (longest diameter to be&#xD;
                  recorded for non-nodal lesions and short axis for nodal lesions) as greater than&#xD;
                  or equal to 20 mm with conventional techniques or as greater than or equal to 10&#xD;
                  mm with spiral computed tomography (CT) scan.&#xD;
&#xD;
               6. All participants except Cohort 6 must have at least one lesion deemed safe to&#xD;
                  biopsy and be willing to undergo a mandatory baseline biopsy. For Cohort 5, the&#xD;
                  second biopsy at progression is mandatory for the responders (Partial Response&#xD;
                  (PR)/Complete Response (CR)/Stable Disease (SD) &gt; 4 months.&#xD;
&#xD;
               7. Participants enrolling in Cohort 6, the recurrent platinum-resistant sporadic&#xD;
                  high grade serous epithelial or high grade endometrioid ovarian cancer group,&#xD;
                  must have a negative family history of HBOC syndrome, or negative gBRCA1/2m test.&#xD;
                  Participants should have recurrent platinum-resistant, defined as disease&#xD;
                  recurrence by imaging within 6 months of the last receipt of platinum-based&#xD;
                  chemotherapy. This cohort should have measurable (defined by Response Evaluation&#xD;
                  Criteria in Solid Tumors (RECIST) v1.1) but without biopsiable disease,&#xD;
                  determined by principal investigator (PI) and Interventional Radiology (e.g.,&#xD;
                  cystic abnormal mass, not safely biopsiable disease). Rising CA125 only is not&#xD;
                  considered as platinum-resistant disease. Participants with primary platinum&#xD;
                  refractory disease defined as progression during or within 3 months after&#xD;
                  receiving first-line platinum-based chemotherapy are not eligible.&#xD;
&#xD;
               8. Participants must be at least 4 weeks from previous therapy (chemotherapy,&#xD;
                  hormonal therapy, and radiation therapy, or investigational agents; 6 weeks for&#xD;
                  mitomycin C).&#xD;
&#xD;
               9. The use of raloxifene, denosumab, or bisphosphonates for bone health is allowed.&#xD;
&#xD;
              10. There is no limit on the number of prior therapies.&#xD;
&#xD;
              11. Participants must be at least 1 week from the last dose of complementary or&#xD;
                  alternative medications.&#xD;
&#xD;
              12. Participants who have had major surgery must be fully recovered and greater than&#xD;
                  or equal to 4 weeks postoperative prior to enrolling on study.&#xD;
&#xD;
              13. Age greater than or equal to 18 years.&#xD;
&#xD;
              14. Eastern Cooperative Oncology Group (ECOG) performance status less than or equal&#xD;
                  to 2.&#xD;
&#xD;
              15. Participants must have normal organ and marrow function (in the absence of&#xD;
                  transfusion 24 hours prior to dosing) as defined below:&#xD;
&#xD;
                  leukocytes greater than or equal to 3,000/mcL&#xD;
&#xD;
                  absolute neutrophil count greater than or equal to 1,500/mcL&#xD;
&#xD;
                  platelets greater than or equal to 100,000/mcL&#xD;
&#xD;
                  hemoglobin greater than or equal to 10mg/dL&#xD;
&#xD;
                  total bilirubin less than or equal to 1.5 X institutional upper limit of normal&#xD;
&#xD;
                  Aspartate aminotransferase (AST) Serum glutamic oxaloacetic transaminase&#xD;
                  (SGOT)/alanine aminotransferase (ALT) Serum glutamic pyruvic transaminase (SGPT)&#xD;
                  less than or equal to 3 X institutional upper limit of normal&#xD;
&#xD;
                  creatinine less than or equal to 1.5 X institutional upper limit of normal&#xD;
&#xD;
                  OR&#xD;
&#xD;
                  measured creatinine clearance greater than or equal to 45 mL/min/1.73 m^2 for&#xD;
                  participants with&#xD;
&#xD;
                  creatinine levels above institutional normal.&#xD;
&#xD;
              16. Potassium (K) should be within the range of greater than or equal to 3.6 mEq/L.&#xD;
&#xD;
              17. Women of childbearing potential must have a negative urine or serum pregnancy&#xD;
                  test within 7 days prior to the start of the study.&#xD;
&#xD;
              18. The effects of Chk1/2 Inhibitor (Prexasertib LY2606368) on the developing human&#xD;
                  fetus are unknown. For this reason, all subjects of reproductive potential must&#xD;
                  agree to use adequate contraception prior to study entry, for the duration of&#xD;
                  study participation, and for at least four months following the last dose of&#xD;
                  experimental therapy. All subjects of reproductive potential must also agree to&#xD;
                  use both a barrier method and a second method of birth control during the course&#xD;
                  of the study and for four months after the last dose of study drug(s). Should a&#xD;
                  woman become pregnant or suspect she is pregnant while she is participating in&#xD;
                  this study, she should inform her treating physician immediately.&#xD;
&#xD;
              19. Ability of subject to understand, adhere to protocol requirements and the&#xD;
                  willingness to sign a written informed consent document.&#xD;
&#xD;
        EXCLUSION CRITERIA:&#xD;
&#xD;
          1. Participants who are receiving any other investigational agents.&#xD;
&#xD;
          2. Participants with known brain metastases should be excluded from this clinical trial&#xD;
             because of their poor prognosis and because they often develop progressive neurologic&#xD;
             dysfunction that would confound the evaluation of neurologic and other adverse events.&#xD;
             Participants with brain metastases diagnosed greater than 1 year prior to study entry&#xD;
             may be considered if they received sterilizing therapy to the central nervous system&#xD;
             (CNS) (resection or radiation) and have been CNS recurrence-free for the 1-year&#xD;
             period.&#xD;
&#xD;
          3. Participants who have had prior treatment with LY2606368 or other Chk inhibitors&#xD;
&#xD;
          4. Participants with a serious cardiac condition, such as congestive heart failure; New&#xD;
             York Heart Association Class III/IV heart disease; unstable angina pectoris;&#xD;
             myocardial infarction within the last 3 months; valvulopathy that is severe, moderate,&#xD;
             or deemed clinically significant despite medical intervention; or arrhythmias that are&#xD;
             symptomatic or refractory to medical intervention.&#xD;
&#xD;
          5. Participants who have corrected QT interval (QTc) interval of &gt; 470 msec on a&#xD;
             screening electrocardiogram.&#xD;
&#xD;
          6. Participants with a prior history of drug-induced serotonin syndrome, or a family&#xD;
             history of long-QT syndrome.&#xD;
&#xD;
          7. Lack of recovery of prior adverse events due to prior cancer therapy to Grade less&#xD;
             than or equal to 1 (National Cancer Institute (NCI) Common Terminology Criteria for&#xD;
             Adverse Events (CTCAE); except alopecia). Electrolyte abnormalities that are corrected&#xD;
             with supplementation will be eligible. Participants with platinum-related grade 2 or&#xD;
             greater hypomagnesemia (on replacement) will be eligible. Stable persistent grade 2&#xD;
             peripheral neuropathy may be allowed as determined on a case-by-case basis at the&#xD;
             discretion of the principal investigator (PI).&#xD;
&#xD;
          8. Uncontrolled intercurrent illness including, but not limited to, symptomatic&#xD;
             congestive heart failure, unstable angina pectoris, cardiac arrhythmia, clinically&#xD;
             significant gastrointestinal (GI) bleeding or hemoptysis within 28 days prior to the&#xD;
             start of the study, or psychiatric illness/social situations that would limit&#xD;
             compliance with study requirements.&#xD;
&#xD;
          9. Participants with active infection will not be eligible but may become eligible once&#xD;
             infection has resolved and they are at least 7 days from completion of antibiotics.&#xD;
&#xD;
         10. Another previous or current invasive malignancy within the last 2 years, with the&#xD;
             exception of curatively treated stage IA cervical carcinoma, or resected stage IA&#xD;
             endometrial cancer, and noninvasive nonmelanoma skin cancers. Participants with&#xD;
             gBRCA1/2m and primary breast or ovarian cancers will be eligible for Cohort 1.&#xD;
&#xD;
         11. Human immunodeficiency virus (HIV)-positive participants on combination antiretroviral&#xD;
             therapy are ineligible because of the potential for pharmacokinetic interactions with&#xD;
             LY2606368. HIV- positive participants who are not on highly active antiretroviral&#xD;
             therapy (HAART) and have cluster of differentiation 4 (CD4) counts &gt; 500 will be&#xD;
             considered on an individual basis.&#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>Jung-Min Lee, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Cancer Institute (NCI)</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>National Institutes of Health Clinical Center, 9000 Rockville Pike</name>
      <address>
        <city>Bethesda</city>
        <state>Maryland</state>
        <zip>20892</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_2014-C-0156.html</url>
    <description>NIH Clinical Center Detailed Web Page</description>
  </link>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>July 29, 2014</study_first_submitted>
  <study_first_submitted_qc>July 29, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 30, 2014</study_first_posted>
  <results_first_submitted>July 14, 2022</results_first_submitted>
  <results_first_submitted_qc>August 11, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">September 10, 2022</results_first_posted>
  <last_update_submitted>August 11, 2022</last_update_submitted>
  <last_update_submitted_qc>August 11, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 10, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>National Cancer Institute (NCI)</investigator_affiliation>
    <investigator_full_name>Jung-Min Lee, M.D.</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>p53 Dysfunction</keyword>
  <keyword>Cell Cycle Arrest</keyword>
  <keyword>Checkpoint Kinases</keyword>
  <keyword>DNA Damage Repair Pathways</keyword>
  <keyword>Hereditary Breast and Ovarian Cancer Syndrome</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</mesh_term>
    <mesh_term>Prostatic Neoplasms</mesh_term>
    <mesh_term>Ovarian Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Ovarian Epithelial</mesh_term>
    <mesh_term>Triple Negative Breast Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prexasertib</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>For All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request.&#xD;
In addition, all large-scale genomic sequencing data will be shared with subscribers to database of Genotypes and Phenotypes (dbGaP).</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_time_frame>Clinical data available during the study and indefinitely. Genomic data are available once genomic data are uploaded per protocol genomic data sharing plan (GDS) for as long as database is active.</ipd_time_frame>
    <ipd_access_criteria>Clinical data will be made available via subscription to Biomedical Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI).&#xD;
Genomic data are made available via the database of Genotypes and Phenotypes (dbGaP) through requests to the data custodians.</ipd_access_criteria>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>December 2, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/13/NCT02203513/Prot_SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form: Standard Consent</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>April 2, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/13/NCT02203513/ICF_001.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form: Cohort: All Participants Consent</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>March 30, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/13/NCT02203513/ICF_002.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>Cohorts 5 &amp; 6 are combined because they are for platinum resistant BRCA wild type high grade serous ovarian cancer (HGSOC) participants, literally the same population. Only difference between the two cohorts is cohort 5 is a research biopsy cohort &amp; cohort 6 had no safely biopsiable disease. Given that Eli Lilly prematurely terminated the study we could not enroll enough number of participants for both cohorts. Thus, it is appropriate and scientifically relevant to report the data in one group.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Cohort 1 Breast/Ovarian Breast Cancer (BRCA) Mutation Positive</title>
          <description>All participants received Prexasertib (LY2606368) 105 mg/m^2 on dose level 1.</description>
        </group>
        <group group_id="P2">
          <title>Cohort 2 Breast/Ovarian Breast Cancer (BRCA) Wild-Type (wt) Cohort</title>
          <description>All participants received Prexasertib (LY2606368) 105 mg/m^2 on dose level 1, except six participants who received Prexasertib 105 mg/m^2 on dose level 1 followed by 80 mg/m^2 on dose level -1. And one participant did not receive drug.</description>
        </group>
        <group group_id="P3">
          <title>Cohort 3 Breast Cancer (BRCA) Wild-Type (wt) Triple Negative Breast Cancer</title>
          <description>All participants received Prexasertib (LY2606368) 105 mg/m^2 on dose level 1, except two participants who received Prexasertib 105 mg/m^2 on dose level 1 followed by 80 mg/m^2 on dose level -1.</description>
        </group>
        <group group_id="P4">
          <title>Cohort 4 Castration-resistant Metastatic Prostate</title>
          <description>One participant received Prexasertib (LY2606368) 105 mg/m^2 on dose level -1 followed by Prexasertib 80 mg/m^2 on dose level -1. And one participant received Prexasertib 105 mg/m^2 on dose level 1.</description>
        </group>
        <group group_id="P5">
          <title>Cohorts 5 and 6 Ovarian Breast Cancer (BRCA) Wild-Type (wt) Platinum-resistant</title>
          <description>All participants received Prexasertib (LY2606368) 105 mg/m^2 on dose level 1, except six participants in cohort 5 received Prexasertib 105 mg/m^2 on dose level 1 followed by 80 mg/m^2 on dose level -1. And three participants on cohort 6 received Prexasertib 105 mg/m^2 on dose level 1 followed by 80 mg/m^2 on dose level -1.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="22"/>
                <participants group_id="P2" count="29"/>
                <participants group_id="P3" count="9"/>
                <participants group_id="P4" count="2"/>
                <participants group_id="P5" count="49"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
                <participants group_id="P2" count="21"/>
                <participants group_id="P3" count="6"/>
                <participants group_id="P4" count="1"/>
                <participants group_id="P5" count="43"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="8"/>
                <participants group_id="P3" count="3"/>
                <participants group_id="P4" count="1"/>
                <participants group_id="P5" count="6"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Refused further treatment</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <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>Switched to alternative treatment</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="4"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Did not receive investigational product (IP)</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death (unrelated to study therapy)</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="1"/>
                <participants group_id="P5" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Cohorts 5 &amp; 6 are combined because they are for platinum resistant BRCA wild type high grade serous ovarian cancer (HGSOC) participants, literally the same population. Only difference between the two cohorts is cohort 5 is a research biopsy cohort &amp; cohort 6 had no safely biopsiable disease. Given that Eli Lilly prematurely terminated the study we could not enroll enough number of participants for both cohorts. Thus, it is appropriate and scientifically relevant to report the data in one group.</population>
      <group_list>
        <group group_id="B1">
          <title>Cohort 1 Breast/Ovarian Breast Cancer (BRCA) Mutation Positive</title>
          <description>All participants received Prexasertib (LY2606368) 105 mg/m^2 on dose level 1.</description>
        </group>
        <group group_id="B2">
          <title>Cohort 2 Breast/Ovarian Breast Cancer (BRCA) Wild-Type (wt) Cohort</title>
          <description>All participants received Prexasertib (LY2606368) 105 mg/m^2 on dose level 1, except six participants who received Prexasertib 105 mg/m^2 on dose level 1 followed by 80 mg/m^2 on dose level -1. And one participant did not receive drug.</description>
        </group>
        <group group_id="B3">
          <title>Cohort 3 Breast Cancer (BRCA) Wild-Type (wt) Triple Negative Breast Cancer</title>
          <description>All participants received Prexasertib (LY2606368) 105 mg/m^2 on dose level 1, except two participants who received Prexasertib 105 mg/m^2 on dose level 1 followed by 80 mg/m^2 on dose level -1.</description>
        </group>
        <group group_id="B4">
          <title>Cohort 4 Castration-resistant Metastatic Prostate</title>
          <description>One participant received Prexasertib (LY2606368) 105 mg/m^2 on dose level -1 followed by Prexasertib 80 mg/m^2 on dose level -1. And one participant received Prexasertib 105 mg/m^2 on dose level 1.</description>
        </group>
        <group group_id="B5">
          <title>Cohorts 5 and 6 Ovarian Breast Cancer (BRCA) Wild-Type (wt) Platinum-resistant</title>
          <description>All participants received Prexasertib (LY2606368) 105 mg/m^2 on dose level 1, except six participants in cohort 5 received Prexasertib 105 mg/m^2 on dose level 1 followed by 80 mg/m^2 on dose level -1. And three participants on cohort 6 received Prexasertib 105 mg/m^2 on dose level 1 followed by 80 mg/m^2 on dose level -1.</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="22"/>
            <count group_id="B2" value="29"/>
            <count group_id="B3" value="9"/>
            <count group_id="B4" value="2"/>
            <count group_id="B5" value="49"/>
            <count group_id="B6" value="111"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="26"/>
                    <measurement group_id="B6" value="64"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="23"/>
                    <measurement group_id="B6" value="47"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="57.32" spread="9.55"/>
                    <measurement group_id="B2" value="64.61" spread="9.52"/>
                    <measurement group_id="B3" value="52.46" spread="15.17"/>
                    <measurement group_id="B4" value="65.6" spread="10.04"/>
                    <measurement group_id="B5" value="62.59" spread="10.84"/>
                    <measurement group_id="B6" value="61.31" spread="11.09"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="22"/>
                    <measurement group_id="B2" value="29"/>
                    <measurement group_id="B3" value="9"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="49"/>
                    <measurement group_id="B6" value="109"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="2"/>
                    <measurement group_id="B6" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="21"/>
                    <measurement group_id="B2" value="28"/>
                    <measurement group_id="B3" value="9"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="47"/>
                    <measurement group_id="B6" value="107"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="3"/>
                    <measurement group_id="B6" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="4"/>
                    <measurement group_id="B6" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                    <measurement group_id="B2" value="27"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="42"/>
                    <measurement group_id="B6" value="94"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="22"/>
                    <measurement group_id="B2" value="29"/>
                    <measurement group_id="B3" value="9"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="49"/>
                    <measurement group_id="B6" value="111"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Objective Response (Complete Response (CR) + Partial Response (PR)</title>
        <description>Objective response (CR+PR) of single agent Prexasertib (LY2606368) in participants with germline BReast CAncer gene -Mutated (gBRCAm)-associated breast and ovarian cancers, high grade serous ovarian cancer (HGSOC) and triple-negative breast cancer (TNBC) at low genetic risk. Response was measured using the Response Evaluation Criteria in Solid Tumors (RECIST)v1.1. Complete Response is disappearance of all target lesions. Partial Response is at least a 30% decrease in the sum of diameters of target lesions.</description>
        <time_frame>Cohorts 1-3, 5, &amp; 6 were restaged every 2 mos. Cohort 4 was restaged every 3 mos. Restaging continued until participant's disease was deemed progressive by RECIST or until removed from treatment for other etiology for an combined average of 133 days.</time_frame>
        <population>Overall, 17 participants were not evaluable for this outcome measure. Overall participants analyzed adjusted to include only evaluable subjects as defined by the protocol (i.e., only those participants who have measurable disease present at baseline, have received at least one cycle of therapy, and have had their disease re-evaluated; Response Evaluation Criteria in Solid Tumors (RECIST) Evaluable).</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1 Breast/Ovarian Breast Cancer (BRCA) Mutation Positive</title>
            <description>All participants received Prexasertib (LY2606368) 105 mg/m^2 on dose level 1.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2 Breast/Ovarian Breast Cancer (BRCA) Wild-Type (wt) Cohort</title>
            <description>All participants received Prexasertib (LY2606368) 105 mg/m^2 on dose level 1, except six participants who received Prexasertib 105 mg/m^2 on dose level 1 followed by 80 mg/m^2 on dose level -1. And one participant did not receive drug.</description>
          </group>
          <group group_id="O3">
            <title>Cohort 3 Breast Cancer (BRCA) Wild-Type (wt) Triple Negative Breast Cancer</title>
            <description>All participants received Prexasertib (LY2606368) 105 mg/m^2 on dose level 1, except two participants who received Prexasertib 105 mg/m^2 on dose level 1 followed by 80 mg/m^2 on dose level -1.</description>
          </group>
          <group group_id="O4">
            <title>Cohort 4 Castration-resistant Metastatic Prostate</title>
            <description>One participant received Prexasertib (LY2606368) 105 mg/m^2 on dose level -1 followed by Prexasertib 80 mg/m^2 on dose level -1. And one participant received Prexasertib 105 mg/m^2 on dose level 1.</description>
          </group>
          <group group_id="O5">
            <title>Cohorts 5 and 6 Ovarian Breast Cancer (BRCA) Wild-Type (wt) Platinum-resistant</title>
            <description>Cohorts 5 and 6 are combined because they are for platinum resistant BRCA wild type high grade serous ovarian cancer (HGSOC) participants, literally the same population. Only difference between the two cohorts is cohort 5 is a research biopsy cohort and cohort 6 had no safely biopsiable disease. Given that Eli Lilly prematurely terminated the study we could not enroll enough number of participants for both cohorts.&#xD;
All participants received Prexasertib (LY2606368) 105 mg/m^2 on dose level 1, except six participants in cohort 5 received Prexasertib 105 mg/m^2 on dose level 1 followed by 80 mg/m^2 on dose level -1. And three participants on cohort 6 received Prexasertib 105 mg/m^2 on dose level 1 followed by 80 mg/m^2 on dose level -1.</description>
          </group>
        </group_list>
        <measure>
          <title>Objective Response (Complete Response (CR) + Partial Response (PR)</title>
          <description>Objective response (CR+PR) of single agent Prexasertib (LY2606368) in participants with germline BReast CAncer gene -Mutated (gBRCAm)-associated breast and ovarian cancers, high grade serous ovarian cancer (HGSOC) and triple-negative breast cancer (TNBC) at low genetic risk. Response was measured using the Response Evaluation Criteria in Solid Tumors (RECIST)v1.1. Complete Response is disappearance of all target lesions. Partial Response is at least a 30% decrease in the sum of diameters of target lesions.</description>
          <population>Overall, 17 participants were not evaluable for this outcome measure. Overall participants analyzed adjusted to include only evaluable subjects as defined by the protocol (i.e., only those participants who have measurable disease present at baseline, have received at least one cycle of therapy, and have had their disease re-evaluated; Response Evaluation Criteria in Solid Tumors (RECIST) Evaluable).</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="26"/>
                <count group_id="O3" value="8"/>
                <count group_id="O4" value="1"/>
                <count group_id="O5" value="39"/>
              </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="2"/>
                    <measurement group_id="O2" value="8"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0).</title>
        <description>Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.</description>
        <time_frame>Participants were followed for the duration of treatment and up to 4 weeks after being off treatment, an average of 7 months</time_frame>
        <population>Cohorts 5 &amp; 6 are combined because they are for platinum resistant BRCA wild type high grade serous ovarian cancer (HGSOC) participants, literally the same population. Only difference between the two cohorts is cohort 5 is a research biopsy cohort &amp; cohort 6 had no safely biopsiable disease. Given that Eli Lilly prematurely terminated the study we could not enroll enough number of participants for both cohorts. Thus, it is appropriate and scientifically relevant to report the data in one group.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1 Breast/Ovarian Breast Cancer (BRCA) Mutation Positive</title>
            <description>All participants received Prexasertib (LY2606368) 105 mg/m^2 on dose level 1.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2 Breast/Ovarian Breast Cancer (BRCA) Wild-Type (wt) Cohort</title>
            <description>All participants received Prexasertib (LY2606368) 105 mg/m^2 on dose level 1, except six participants who received Prexasertib 105 mg/m^2 on dose level 1 followed by 80 mg/m^2 on dose level -1. And one participant did not receive drug.</description>
          </group>
          <group group_id="O3">
            <title>Cohort 3 Breast Cancer (BRCA) Wild-Type (wt) Triple Negative Breast Cancer</title>
            <description>All participants received Prexasertib (LY2606368) 105 mg/m^2 on dose level 1, except two participants who received Prexasertib 105 mg/m^2 on dose level 1 followed by 80 mg/m^2 on dose level -1.</description>
          </group>
          <group group_id="O4">
            <title>Cohorts 5 and 6 Ovarian Breast Cancer (BRCA) Wild-Type (wt) Platinum-resistant</title>
            <description>Cohorts 5 and 6 are combined because they are for platinum resistant BRCA wild type high grade serous ovarian cancer (HGSOC) participants, literally the same population. Only difference between the two cohorts is cohort 5 is a research biopsy cohort and cohort 6 had no safely biopsiable disease. Given that Eli Lilly prematurely terminated the study we could not enroll enough number of participants for both cohorts.&#xD;
All participants received Prexasertib (LY2606368) 105 mg/m^2 on dose level 1, except six participants in cohort 5 received Prexasertib 105 mg/m^2 on dose level 1 followed by 80 mg/m^2 on dose level -1. And three participants on cohort 6 received Prexasertib 105 mg/m^2 on dose level 1 followed by 80 mg/m^2 on dose level -1.</description>
          </group>
          <group group_id="O5">
            <title>Cohorts 5 and 6 Breast Cancer (BRCA) Wild-Type (wt) Platinum Resistant Cohort</title>
            <description>All participants received Prexasertib (LY2606368) 105 mg/m^2 on dose level 1, except four participants in cohort 5 received Prexasertib 105 mg/m^2 on dose level 1 followed by 80 mg/m^2 on dose level -1. And one participant on cohort 6 received Prexasertib 105 mg/m^2 on dose level 1 followed by 80 mg/m^2 on dose level -1.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0).</title>
          <description>Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.</description>
          <population>Cohorts 5 &amp; 6 are combined because they are for platinum resistant BRCA wild type high grade serous ovarian cancer (HGSOC) participants, literally the same population. Only difference between the two cohorts is cohort 5 is a research biopsy cohort &amp; cohort 6 had no safely biopsiable disease. Given that Eli Lilly prematurely terminated the study we could not enroll enough number of participants for both cohorts. Thus, it is appropriate and scientifically relevant to report the data in one group.</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="22"/>
                <count group_id="O2" value="29"/>
                <count group_id="O3" value="9"/>
                <count group_id="O4" value="2"/>
                <count group_id="O5" value="49"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22"/>
                    <measurement group_id="O2" value="29"/>
                    <measurement group_id="O3" value="9"/>
                    <measurement group_id="O4" value="2"/>
                    <measurement group_id="O5" value="49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Participants were followed for the duration of treatment and up to 4 weeks after being off treatment, an average of 7 months.</time_frame>
      <desc>Cohorts 5 &amp; 6 are combined because they are for platinum resistant BRCA wild type high grade serous ovarian cancer (HGSOC) participants, literally the same population. Only difference between the two cohorts is cohort 5 is a research biopsy cohort &amp;cohort 6 had no safely biopsiable disease. Given that Eli Lilly prematurely terminated the study we could not enroll enough number of participants for both cohorts. Thus, it is appropriate and scientifically relevant to report the data in one group.</desc>
      <group_list>
        <group group_id="E1">
          <title>Cohort 1 Breast/Ovarian Breast Cancer (BRCA) Mutation Positive</title>
          <description>All participants received Prexasertib (LY2606368) 105 mg/m^2 on dose level 1.</description>
        </group>
        <group group_id="E2">
          <title>Cohort 2 Breast/Ovarian Breast Cancer (BRCA) Wild-Type (wt) Cohort</title>
          <description>All participants received Prexasertib (LY2606368) 105 mg/m^2 on dose level 1, except six participants who received Prexasertib 105 mg/m^2 on dose level 1 followed by 80 mg/m^2 on dose level -1. And one participant did not receive drug.</description>
        </group>
        <group group_id="E3">
          <title>Cohort 3 Breast Cancer (BRCA) Wild-Type (wt) Triple Negative Breast Cancer</title>
          <description>All participants received Prexasertib (LY2606368) 105 mg/m^2 on dose level 1, except two participants who received Prexasertib 105 mg/m^2 on dose level 1 followed by 80 mg/m^2 on dose level -1.</description>
        </group>
        <group group_id="E4">
          <title>Cohort 4 Castration-resistant Metastatic Prostate</title>
          <description>One participant received Prexasertib (LY2606368) 105 mg/m^2 on dose level -1 followed by Prexasertib 80 mg/m^2 on dose level -1. And one participant received Prexasertib 105 mg/m^2 on dose level 1.</description>
        </group>
        <group group_id="E5">
          <title>Cohorts 5 and 6 Ovarian Breast Cancer (BRCA) Wild-Type (wt) Platinum-resistant</title>
          <description>All participants received Prexasertib (LY2606368) 105 mg/m^2 on dose level 1, except six participants in cohort 5 received Prexasertib 105 mg/m^2 on dose level 1 followed by 80 mg/m^2 on dose level -1. And three participants on cohort 6 received Prexasertib 105 mg/m^2 on dose level 1 followed by 80 mg/m^2 on dose level -1.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>CTCAE (4.0)</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="1" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="29"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="29"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="28" subjects_at_risk="49"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="5" subjects_affected="4" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Febrile neutropenia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="9" subjects_affected="7" subjects_at_risk="49"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Chest pain - cardiac</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Sinus tachycardia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal distension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="22"/>
                <counts group_id="E2" events="5" subjects_affected="3" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" events="5" subjects_affected="4" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Ascites</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="3" subjects_affected="2" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Colonic obstruction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="3" subjects_affected="3" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="4" subjects_affected="3" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="3" subjects_affected="2" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Ileus</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Jejunal obstruction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Lower gastrointestinal hemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="4" subjects_affected="3" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Small intestinal obstruction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="4" subjects_affected="4" subjects_at_risk="49"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Edema limbs</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="3" subjects_affected="2" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="7" subjects_affected="7" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Flu like symptoms</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Infusion related reaction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="3" subjects_affected="3" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Skin infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="3" subjects_affected="3" subjects_at_risk="49"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Creatinine increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="29"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="5" subjects_affected="3" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="9" subjects_affected="5" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>White blood cell decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="3" subjects_affected="2" subjects_at_risk="49"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="4" subjects_affected="2" subjects_at_risk="49"/>
              </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="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Flank pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Musculoskeletal and connective tissue disorder - Other, Paralysis of lower extremities</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Myelodysplastic syndrome</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, Death</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, Specify</sub_title>
                <description>Death from progressive disease (PD)</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, Disease progression</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, PD</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </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="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Intracranial hemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Peripheral motor neuropathy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Seizure</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Hematuria</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="3" subjects_affected="3" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Urinary tract obstruction</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="4" subjects_affected="3" subjects_at_risk="49"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Vaginal hemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </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="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" events="3" subjects_affected="2" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Hoarseness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="5" subjects_affected="5" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Pneumothorax</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Respiratory failure</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Respiratory, thoracic and mediastinal disorders - Other, Pneumonia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Wheezing</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Skin and subcutaneous tissue disorders - Other, Cellulitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="49"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hematoma</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Thromboembolic event</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>CTCAE (4.0)</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="22" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="29" subjects_at_risk="29"/>
                <counts group_id="E3" subjects_affected="9" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="49" subjects_at_risk="49"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" events="81" subjects_affected="22" subjects_at_risk="22"/>
                <counts group_id="E2" events="158" subjects_affected="26" subjects_at_risk="29"/>
                <counts group_id="E3" events="39" subjects_affected="9" subjects_at_risk="9"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="2"/>
                <counts group_id="E5" events="256" subjects_affected="44" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Blood and lymphatic system disorders - Other, Petechia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Blood and lymphatic system disorders - Other, Thrombocytosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Febrile neutropenia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Leukocytosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Chest pain - cardiac</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="5" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Electrocardiogram QT corrected interval prolonged</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="2" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Heart failure</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Palpitations</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="4" subjects_affected="4" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Restrictive cardiomyopathy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Sinus bradycardia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="5" subjects_affected="3" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Sinus tachycardia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="9" subjects_affected="5" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="49"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Ear pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Vertigo</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperthyroidism</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Hypothyroidism</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Blurred vision</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Conjunctivitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Dry eye</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Eye disorders - Other, Eye infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Eye disorders - Other, Eye ptosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Eye disorders - Other, Infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal distension</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="12" subjects_affected="9" subjects_at_risk="22"/>
                <counts group_id="E2" events="19" subjects_affected="13" subjects_at_risk="29"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" events="40" subjects_affected="23" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Ascites</sub_title>
                <counts group_id="E1" events="11" subjects_affected="4" subjects_at_risk="22"/>
                <counts group_id="E2" events="40" subjects_affected="5" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="10" subjects_affected="6" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Bloating</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="10" subjects_affected="7" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Colitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="13" subjects_affected="10" subjects_at_risk="22"/>
                <counts group_id="E2" events="12" subjects_affected="9" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="2" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" events="18" subjects_affected="14" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="7" subjects_affected="5" subjects_at_risk="22"/>
                <counts group_id="E2" events="24" subjects_affected="14" subjects_at_risk="29"/>
                <counts group_id="E3" events="5" subjects_affected="4" subjects_at_risk="9"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="2"/>
                <counts group_id="E5" events="46" subjects_affected="26" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Esophagitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Fecal incontinence</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Flatulence</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Gastritis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Gastroesophageal reflux disease</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="7" subjects_affected="6" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Gastrointestinal disorders - Other, Early satiety</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Gastrointestinal disorders - Other, Hematochezia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Gastrointestinal disorders - Other, Mouth Sore</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Gastrointestinal disorders - Other, Mouth ulcer</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Gastrointestinal disorders - Other, Rectal bleeding</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Gastrointestinal disorders - Other, tenesmus</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Hemorrhoids</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Lower gastrointestinal hemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="3" subjects_affected="2" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Mucositis oral</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" events="3" subjects_affected="2" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="15" subjects_affected="11" subjects_at_risk="22"/>
                <counts group_id="E2" events="27" subjects_affected="20" subjects_at_risk="29"/>
                <counts group_id="E3" events="5" subjects_affected="3" subjects_at_risk="9"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="2"/>
                <counts group_id="E5" events="47" subjects_affected="28" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Obstruction gastric</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Oral hemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="4" subjects_affected="4" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Periodontal disease</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Rectal hemorrhage</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Rectal pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Small intestinal obstruction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Toothache</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="6" subjects_affected="5" subjects_at_risk="22"/>
                <counts group_id="E2" events="21" subjects_affected="13" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" events="26" subjects_affected="13" subjects_at_risk="49"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" events="6" subjects_affected="3" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="7" subjects_affected="5" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Edema limbs</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="29"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" events="15" subjects_affected="12" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Edema trunk</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Facial pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="21" subjects_affected="10" subjects_at_risk="22"/>
                <counts group_id="E2" events="29" subjects_affected="19" subjects_at_risk="29"/>
                <counts group_id="E3" events="7" subjects_affected="6" subjects_at_risk="9"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" events="72" subjects_affected="39" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" events="17" subjects_affected="9" subjects_at_risk="22"/>
                <counts group_id="E2" events="13" subjects_affected="9" subjects_at_risk="29"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="24" subjects_affected="13" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Flu like symptoms</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="7" subjects_affected="7" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Gait disturbance</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Infusion related reaction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="4" subjects_affected="3" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Localized edema</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="7" subjects_affected="6" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="22"/>
                <counts group_id="E2" events="5" subjects_affected="4" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" events="9" subjects_affected="8" subjects_at_risk="49"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Cholecystitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Allergic reaction</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="3" subjects_affected="2" subjects_at_risk="49"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Gum infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Infections and infestations - Other, Thrush</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Infections and infestations - Other, Viral origin-shingles</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Infections and infestations - Other, Zoster</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="3" subjects_affected="2" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Mucosal infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Peritoneal infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Pharyngitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Rhinitis infective</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Skin infection</sub_title>
                <counts group_id="E1" events="6" subjects_affected="3" subjects_at_risk="22"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="29"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="4" subjects_affected="2" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Tooth infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Upper respiratory infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="7" subjects_affected="5" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="7" subjects_affected="5" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="22"/>
                <counts group_id="E2" events="7" subjects_affected="5" subjects_at_risk="29"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="29" subjects_affected="14" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Vulval infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Wound infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Bruising</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="4" subjects_affected="4" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Dermatitis radiation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="3" subjects_affected="3" subjects_at_risk="49"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Activated partial thromboplastin time prolonged</sub_title>
                <counts group_id="E1" events="16" subjects_affected="6" subjects_at_risk="22"/>
                <counts group_id="E2" events="33" subjects_affected="15" subjects_at_risk="29"/>
                <counts group_id="E3" events="8" subjects_affected="6" subjects_at_risk="9"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" events="3" subjects_affected="1" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="9" subjects_affected="5" subjects_at_risk="22"/>
                <counts group_id="E2" events="7" subjects_affected="6" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="16" subjects_affected="13" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Alkaline phosphatase increased</sub_title>
                <counts group_id="E1" events="12" subjects_affected="9" subjects_at_risk="22"/>
                <counts group_id="E2" events="26" subjects_affected="11" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" events="26" subjects_affected="19" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="12" subjects_affected="7" subjects_at_risk="22"/>
                <counts group_id="E2" events="7" subjects_affected="5" subjects_at_risk="29"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="17" subjects_affected="10" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Creatinine increased</sub_title>
                <counts group_id="E1" events="10" subjects_affected="7" subjects_at_risk="22"/>
                <counts group_id="E2" events="30" subjects_affected="11" subjects_at_risk="29"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" events="27" subjects_affected="15" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Lipase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" events="85" subjects_affected="17" subjects_at_risk="22"/>
                <counts group_id="E2" events="159" subjects_affected="26" subjects_at_risk="29"/>
                <counts group_id="E3" events="37" subjects_affected="8" subjects_at_risk="9"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" events="205" subjects_affected="41" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Lymphocyte count increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="8" subjects_affected="2" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" events="59" subjects_affected="19" subjects_at_risk="22"/>
                <counts group_id="E2" events="138" subjects_affected="27" subjects_at_risk="29"/>
                <counts group_id="E3" events="27" subjects_affected="8" subjects_at_risk="9"/>
                <counts group_id="E4" events="4" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" events="99" subjects_affected="44" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" events="74" subjects_affected="17" subjects_at_risk="22"/>
                <counts group_id="E2" events="168" subjects_affected="24" subjects_at_risk="29"/>
                <counts group_id="E3" events="29" subjects_affected="9" subjects_at_risk="9"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" events="244" subjects_affected="46" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Serum amylase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Weight gain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Weight loss</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="22"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" events="13" subjects_affected="10" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>White blood cell decreased</sub_title>
                <counts group_id="E1" events="76" subjects_affected="19" subjects_at_risk="22"/>
                <counts group_id="E2" events="179" subjects_affected="28" subjects_at_risk="29"/>
                <counts group_id="E3" events="35" subjects_affected="9" subjects_at_risk="9"/>
                <counts group_id="E4" events="2" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" events="47" subjects_affected="44" subjects_at_risk="49"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" events="9" subjects_affected="7" subjects_at_risk="22"/>
                <counts group_id="E2" events="9" subjects_affected="8" subjects_at_risk="29"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="2"/>
                <counts group_id="E5" events="17" subjects_affected="16" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" events="7" subjects_affected="7" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Hypercalcemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E2" events="4" subjects_affected="3" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="8" subjects_affected="4" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Hyperkalemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="4" subjects_affected="3" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Hypermagnesemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E2" events="8" subjects_affected="6" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="3" subjects_affected="3" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Hypernatremia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Hyperuricemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="3" subjects_affected="2" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Hypoalbuminemia</sub_title>
                <counts group_id="E1" events="13" subjects_affected="10" subjects_at_risk="22"/>
                <counts group_id="E2" events="33" subjects_affected="9" subjects_at_risk="29"/>
                <counts group_id="E3" events="3" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" events="25" subjects_affected="13" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Hypocalcemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="29"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" events="3" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" events="5" subjects_affected="3" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Hypoglycemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" events="6" subjects_affected="3" subjects_at_risk="22"/>
                <counts group_id="E2" events="8" subjects_affected="5" subjects_at_risk="29"/>
                <counts group_id="E3" events="3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" events="15" subjects_affected="10" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Hypomagnesemia</sub_title>
                <counts group_id="E1" events="10" subjects_affected="7" subjects_at_risk="22"/>
                <counts group_id="E2" events="15" subjects_affected="6" subjects_at_risk="29"/>
                <counts group_id="E3" events="6" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" events="64" subjects_affected="22" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="22"/>
                <counts group_id="E2" events="17" subjects_affected="11" subjects_at_risk="29"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="9" subjects_affected="7" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Hypophosphatemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="6" subjects_affected="6" subjects_at_risk="29"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="6" subjects_affected="4" subjects_at_risk="49"/>
              </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="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="3" subjects_affected="3" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Arthritis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="12" subjects_affected="8" subjects_at_risk="22"/>
                <counts group_id="E2" events="7" subjects_affected="6" subjects_at_risk="29"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" events="21" subjects_affected="14" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Bone pain</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="9" subjects_affected="8" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Buttock pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Chest wall pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="4" subjects_affected="4" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Flank pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="10" subjects_affected="8" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Generalized muscle weakness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Joint effusion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Joint range of motion decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Muscle weakness lower limb</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Muscle weakness upper limb</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Musculoskeletal and connective tissue disorder - Other, Right lower extremity</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Musculoskeletal and connective tissue disorder - Other, lower extremity</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="5" subjects_affected="4" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Neck pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="4" subjects_affected="4" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" events="7" subjects_affected="4" subjects_at_risk="22"/>
                <counts group_id="E2" events="4" subjects_affected="3" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="9" subjects_affected="6" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="8" subjects_affected="7" subjects_at_risk="49"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, Fluid from mass</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, Specify</sub_title>
                <description>Thyroid adenomatoid nodule, R lobe</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Tumor pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="3" subjects_affected="2" subjects_at_risk="49"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Cognitive disturbance</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Concentration impairment</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="22"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="11" subjects_affected="8" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Extrapyramidal disorder</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E2" events="6" subjects_affected="6" subjects_at_risk="29"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="11" subjects_affected="6" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Nervous system disorders - Other, Cauda Equina Syndrome 2/2 bone lesions</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Nervous system disorders - Other, L chin weakness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Paresthesia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Peripheral motor neuropathy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="5" subjects_affected="4" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Peripheral sensory neuropathy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="2" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Agitation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="8" subjects_affected="7" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="6" subjects_affected="4" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="8" subjects_affected="8" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Mania</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </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="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Cystitis noninfective</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Hematuria</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="8" subjects_affected="5" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Proteinuria</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="4" subjects_affected="4" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Renal and urinary disorders - Other, Dysuria</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Renal and urinary disorders - Other, Hydronephrosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Renal and urinary disorders - Other, Nitrite positive urine</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Renal and urinary disorders - Other, nocturia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Renal calculi</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Urinary frequency</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Urinary incontinence</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Urinary retention</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Urinary tract obstruction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Urinary tract pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="49"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspareunia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Gynecomastia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Pelvic pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Perineal pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Vaginal discharge</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="3" subjects_affected="3" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Vaginal dryness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Vaginal hemorrhage</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="3" subjects_affected="3" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Vaginal pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Allergic rhinitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Aspiration</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Atelectasis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="22"/>
                <counts group_id="E2" events="8" subjects_affected="7" subjects_at_risk="29"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="9" subjects_affected="9" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="22"/>
                <counts group_id="E2" events="11" subjects_affected="9" subjects_at_risk="29"/>
                <counts group_id="E3" events="4" subjects_affected="3" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="22" subjects_affected="15" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="6" subjects_affected="4" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Hiccups</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Hoarseness</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="4" subjects_affected="3" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Pericardial effusion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="29"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="10" subjects_affected="8" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Postnasal drip</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Pulmonary edema</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Respiratory, thoracic and mediastinal disorders - Other, Throat tightness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Sore throat</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E2" events="7" subjects_affected="6" subjects_at_risk="29"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="9" subjects_affected="8" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Wheezing</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Bullous dermatitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Erythema multiforme</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Hyperhidrosis</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="3" subjects_affected="3" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Papulopustular rash</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Photosensitivity</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Rash acneiform</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" events="7" subjects_affected="4" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" events="6" subjects_affected="6" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Skin and subcutaneous tissue disorders - Other, Abrasion of LUE</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Skin and subcutaneous tissue disorders - Other, Cellulitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Skin and subcutaneous tissue disorders - Other, Dermatitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Skin and subcutaneous tissue disorders - Other, Eccchymosis on forearm</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Skin and subcutaneous tissue disorders - Other, Ecchymosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Skin and subcutaneous tissue disorders - Other, Herpes zoster</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Skin and subcutaneous tissue disorders - Other, Laceration</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Skin and subcutaneous tissue disorders - Other, Petechiae</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Skin and subcutaneous tissue disorders - Other, oral blister</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Skin ulceration</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="49"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Surgical and medical procedures - Other, Biliary stent placed</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Flushing</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Hematoma</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Hot flashes</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="8" subjects_affected="5" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Lymphedema</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Thromboembolic event</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Vascular disorders - Other, Pulmonary embolism</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="49"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Jung-min Lee</name_or_title>
      <organization>National Cancer Institute</organization>
      <phone>240-760-6128</phone>
      <email>leej6@mail.nih.gov</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/NCT02203513
org study id: 140156
secondary id: 14-C-0156
nct id: NCT02203513
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
Background:

        -  All cells go through cycles which allow them to divide. In normal cells, checkpoint
           kinase 1 (Chk1) and checkpoint kinase 2 (Chk2) (CHEK 2 (Chk1/2) stop cell division at
           various points to allow any damage to deoxyribonucleic acid (DNA) to be repaired.

        -  When Chk1/2 are not present, cells stop dividing and eventually die. Chk1/2 Inhibitor
           (Prexasertib (LY2606368) blocks the Chk1/2 proteins.

        -  Researchers hope that by blocking Chk1/2, it will cause tumor cells to die, thereby
           shrinking tumors.

      Objective:

      - To see if LY2606368 helps shrink tumors in patients with certain breast, ovarian or
      prostate cancers.

      Eligibility:

      - Participants at least 18 years old with breast or ovarian cancer. They must have a mutation
      in BRCA1 BReast CAncer gene 1 and BRCA2 BReast CAncer gene 2 (BRCA1/2) genes for group 1,
      high grade serious ovarian cancer without BRCA1/2 mutation for group 2, or triple negative
      breast cancer without BRCA1/2 mutation for group 3, or prostate cancer with or without
      BRCA1/2 mutation for group 4.

      Design:

        -  Participants will be screened with a medical history and physical exam. They will have
           blood tests, an electrocardiogram (ECG) heart test, scans, and X-rays. They will have a
           piece of their tumor removed at entry (computed tomography (CT)-assisted biopsy).

        -  Study Day 1: Participants will have a physical exam and blood drawn. They may have a CT
           scan of the chest, abdomen, and pelvis.

        -  Day 1 and Day 15 of each 28-day cycle: Participants will receive the study drug through
           an intravenous (IV).

        -  Vital signs will be checked before and after. An ECG will be done within 1 hour after.

        -  Day 15 and Day 28: Participants will have a physical exam, blood drawn, and a 12 lead
           ECG.

        -  Cycle 1: Participants will have weekly phone calls and blood draws. Participants may
           have another CT-assisted biopsy at the end of cycle 1.

        -  Cycle 2 and beyond, blood will be drawn every other week for routine blood tests.

        -  Participants will have an after-study visit with a physical exam and blood tests.
           Participants may have another biopsy when they progressed on treatment. They will have
           scans of the chest, pelvis, and abdomen and a 12 lead ECG.
Background:

        -  Checkpoint kinases 1 and 2 (Chk1/2) are major regulators of the cell cycle and are
           intimately associated with the cellular response to deoxyribonucleic acid (DNA) damage
           and repair. Chk1/2 also function as the primary mediators of cell cycle arrest in tumors
           with tumor protein P53 (p53) dysfunction, such as high-grade serous ovarian cancer
           (HGSOC), and triple negative breast cancer (TNBC).

        -  Participants with germline BRCA1 BReast CAncer gene 1 and BRCA2 BReast CAncer gene 2
           (BRCA1/2) mutation have inherent defects in DNA damage repair pathways.

        -  Chk1/2 inhibition alone yielded DNA damage and mitotic catastrophe preclinically, even
           in the absence of DNA damage by external agents in tumors with underlying DNA repair
           dysfunction.

        -  The second-generation Chk1/2 inhibitor (Prexasertib (LY2606368) yielded safety and
           preliminary single agent activity in advanced cancer participants.

        -  We hypothesize that LY2606368 will result in clinical benefit in participants with
           Germline BRCA-Mutated (gBRCAm)-associated breast or ovarian cancers, and HGSOC and TNBC
           with low genetic risk.

      Objectives:

        -  To determine the objective response rate (Complete Response (CR)+Partial Response (PR)
           of single agent LY2606368 in patients with gBRCAm-associated breast or ovarian cancer,
           HGSOC and TNBC with low genetic risk.

        -  To determine the safety and toxicity, and progression-free interval (PFI) of LY2606368
           in pretreated participants.

        -  To determine biochemical changes in the DNA damage repair and cell cycle check point
           pathways in tumor and blood samples in response to treatment.

        -  To determine potential resistance mechanisms to LY2606368 treatment in HGSOC.

      Eligibility:

        -  Participants with recurrent/refractory BReast CAncer gene (BRCA) mutant breast or
           ovarian cancer, HGSOC, and TNBC, for whom there remains no standard curative measures.

        -  A documented deleterious germline or somatic BRCA mutation for breast or ovarian cancer
           participants enrolling in Cohort 1.

        -  Negative BRCA mutation testing or negative family history of hereditary breast and
           ovarian cancer syndrome for HGSOC (Cohort 2).

        -  Negative BRCA mutation testing or negative family history of hereditary breast and
           ovarian cancer syndrome for TNBC (Cohort 3).

        -  Effective with amendment I (version date 4/24/2017), Metastatic Castration-Resistant
           Prostate Cancer (mCRPC), Cohort 4 was closed.

        -  Negative BRCA mutation testing or negative family history of hereditary breast and
           ovarian cancer syndrome for recurrent platinum-resistant HGSOC with measurable and
           biopsiable disease (Cohort 5).

        -  Negative BRCA mutation testing or negative family history of hereditary breast and
           ovarian cancer syndrome for recurrent platinum-resistant HGSOC with measurable but
           without biopsiable disease (Cohort 6).

        -  Participants must be off prior chemotherapy, radiation therapy, hormonal therapy, or
           biological therapy for at least 4 weeks.

        -  Eastern Cooperative Oncology Group (ECOG) performance status 0-2 and adequate organ and
           marrow function.

      Design:

        -  This is an open label, single arm phase II trial to examine activity of LY2606368 in
           participants in the 6 independent cohorts (Cohorts 1-6).

        -  LY2606368 will be dosed at the recommended phase 2 dose (RP2D) of 105 mg/m^2 intravenous
           (IV) once every 14 days of a 28 day-cycle.

        -  Research samples including whole blood, circulating tumor cells (CTCs), and tumor
           biopsies will be obtained for pharmacodynamics (PD) endpoints at baseline, Cycle 1 Day
           15 (6-24hour (hr) post-2nd dose), and/or at progression in all participants. Tumor
           biopsies will not be performed in Cohort 6.

        -  Participants (Cohorts 1-3, 5 and 6) will be evaluated every two cycles for response
           using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and every cycle for
           safety using Common Terminology Criteria for Adverse Events (CTCAE) v4.0.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Objective Response (Complete Response (CR) + Partial Response (PR)
time frame: Cohorts 1-3, 5, & 6 were restaged every 2 mos. Cohort 4 was restaged every 3 mos. Restaging continued until participant's disease was deemed progressive by RECIST or until removed from treatment for other etiology for an combined average of 133 days.
description: Objective response (CR+PR) of single agent Prexasertib (LY2606368) in participants with germline BReast CAncer gene -Mutated (gBRCAm)-associated breast and ovarian cancers, high grade serous ovarian cancer (HGSOC) and triple-negative breast cancer (TNBC) at low genetic risk. Response was measured using the Response Evaluation Criteria in Solid Tumors (RECIST)v1.1. Complete Response is disappearance of all target lesions. Partial Response is at least a 30% decrease in the sum of diameters of target lesions.
measure: Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0).
time frame: Participants were followed for the duration of treatment and up to 4 weeks after being off treatment, an average of 7 months
description: Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
arm group label: Arm 1-Prexasertib
arm group type: Experimental
description: Prexasertib (LY2606368) monotherapy treatment
intervention type: Drug
intervention name: LY2606368
description: 105 mg/m^2 intravenous (IV) once every 14 days of a 28 day cycle
arm group label: Arm 1-Prexasertib
other name: Prexasertib
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jung-Min Lee, M.D.
role: Principal Investigator
affiliation: National Cancer Institute (NCI)
facility: 
country: United States
url: https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_2014-C-0156.html
description: NIH Clinical Center Detailed Web Page
responsible party type: Principal Investigator
investigator affiliation: National Cancer Institute (NCI)
investigator full name: Jung-Min Lee, M.D.
investigator title: Principal Investigator
mesh term: Breast Neoplasms
mesh term: Prostatic Neoplasms
mesh term: Ovarian Neoplasms
mesh term: Carcinoma, Ovarian Epithelial
mesh term: Triple Negative Breast Neoplasms
mesh term: Prexasertib
sharing ipd: Yes
ipd description: For All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request.
In addition, all large-scale genomic sequencing data will be shared with subscribers to database of Genotypes and Phenotypes (dbGaP).
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd time frame: Clinical data available during the study and indefinitely. Genomic data are available once genomic data are uploaded per protocol genomic data sharing plan (GDS) for as long as database is active.
ipd access criteria: Clinical data will be made available via subscription to Biomedical Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI).
Genomic data are made available via the database of Genotypes and Phenotypes (dbGaP) through requests to the data custodians.
provided document: 
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 