<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/NCT02975882</url>
  </required_header>
  <id_info>
    <org_study_id>ADVL1514</org_study_id>
    <secondary_id>NCI-2016-01412</secondary_id>
    <secondary_id>ADVL1514</secondary_id>
    <secondary_id>ADVL1514</secondary_id>
    <secondary_id>ADVL1514</secondary_id>
    <secondary_id>UM1CA097452</secondary_id>
    <nct_id>NCT02975882</nct_id>
  </id_info>
  <brief_title>Nanoparticle Albumin-Bound Rapamycin, Temozolomide, and Irinotecan Hydrochloride in Treating Pediatric Patients With Recurrent or Refractory Solid Tumors</brief_title>
  <official_title>A Phase 1 Study of ABI-009 (NAB-RAPAMYCIN) in Pediatric Patients With Recurrent or Refractory Solid Tumors, Including CNS Tumors as a Single Agent and in Combination With Temozolomide and Irinotecan</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Children's Oncology Group</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Children's Oncology Group</source>
  <oversight_info>
    <has_dmc>Yes</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>
      This phase I trial studies the side effects and best dose of nanoparticle albumin-bound&#xD;
      rapamycin when given together with temozolomide and irinotecan hydrochloride in treating&#xD;
      pediatric patients with solid tumors that have come back after treatment and a period of time&#xD;
      during which the tumor could not be detected or has not responded to treatment. Nanoparticle&#xD;
      albumin-bound rapamycin may stop the growth of tumor cells by blocking some of the enzymes&#xD;
      needed for cell growth. Chemotherapy drugs, such as temozolomide and irinotecan&#xD;
      hydrochloride, work in different ways to stop the growth of tumor cells, either by killing&#xD;
      the cells, by stopping them from dividing, or by stopping them from spreading. Giving&#xD;
      nanoparticle albumin-bound rapamycin, temozolomide, and irinotecan hydrochloride may cause&#xD;
      the cancer to stop growing or shrink for a period of time and may lessen the symptoms that&#xD;
      are caused by the cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To estimate the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of&#xD;
      nanoparticle albumin-bound rapamycin (ABI-009) administered as an intravenous infusion over&#xD;
      30 minutes on days 1 and 8 of a 21-day cycle, in combination with temozolomide and irinotecan&#xD;
      hydrochloride (irinotecan) (administered on days 1-5) in pediatric patients with recurrent or&#xD;
      refractory solid tumors, including central nervous system (CNS) tumors.&#xD;
&#xD;
      II. To define and describe the toxicities of single-agent ABI-009 administered as an&#xD;
      intravenous infusion over 30 minutes on days 1 and 8 of a 21-day cycle in pediatric patients&#xD;
      with recurrent or refractory solid tumors, including CNS tumors.&#xD;
&#xD;
      III. To define and describe the toxicities of ABI-009 administered as an intravenous infusion&#xD;
      over 30 minutes on days 1 and 8 of a 21-day cycle in combination with temozolomide and&#xD;
      irinotecan (administered on days 1-5) in pediatric patients with recurrent or refractory&#xD;
      solid tumors, including CNS tumors.&#xD;
&#xD;
      IV. To characterize the pharmacokinetics of ABI-009 in pediatric patients with recurrent or&#xD;
      refractory solid tumors, including CNS tumors.&#xD;
&#xD;
      SECONDARY OBJECTIVE:&#xD;
&#xD;
      I. To preliminarily define the antitumor activity of ABI-009 in combination with temozolomide&#xD;
      and irinotecan within the confines of a phase 1 study.&#xD;
&#xD;
      EXPLORATORY OBJECTIVE:&#xD;
&#xD;
      I. To assess the biologic activity of ABI-009 by examining S6K1 and 4E-BP1 expression status&#xD;
      in archival tumor tissue from solid tumor pediatric patients using immunohistochemistry.&#xD;
&#xD;
      OUTLINE: This is a dose-escalation study of nanoparticle albumin-bound rapamycin.&#xD;
&#xD;
      Patients receive nanoparticle albumin-bound rapamycin intravenously (IV) over 30 minutes on&#xD;
      days 1 and 8 beginning on cycle 1. Patients also receive temozolomide orally (PO) and&#xD;
      irinotecan hydrochloride PO on days 1-5 beginning on cycle 2. Treatment repeats every 21 days&#xD;
      for up to 35 cycles in the absence of disease progression or unacceptable toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up periodically.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">July 24, 2017</start_date>
  <completion_date type="Anticipated">March 31, 2024</completion_date>
  <primary_completion_date type="Actual">March 31, 2022</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <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>Number of Patients With Cycle 1 and 2 Dose Limiting Toxicities Attributable to Nanoparticle Albumin-bound Rapamycin</measure>
    <time_frame>Up to 42 days</time_frame>
    <description>Number of patients with cycle 1 and 2 dose limiting toxicities possibly, probably, or definitely attributable with nanoparticle albumin-bound rapamycin stratified by dose level.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Patients With Adverse Events</measure>
    <time_frame>Up to 24 months</time_frame>
    <description>The number of patients with adverse events that are at least possibly attributable to nanoparticle albumin-bound rapamycin stratified by dose level.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Serum of Nanoparticle Albumin-bound Rapamycin Concentration Curve</measure>
    <time_frame>Days 1, 2, 3, 4, and 8</time_frame>
    <description>Median with minimum and maximum values of the area under the drug concentration over time curve stratified by dose level.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Patients With Antitumor Activity of Nanoparticle Albumin-bound Rapamycin</measure>
    <time_frame>Up to 24 months</time_frame>
    <description>The number of response-evaluable patients with best overall response of complete response (CR), disappearance of all target lesions; or partial response (PR), &gt;=50% decrease in the sum of the products of the two perpendicular diameters of all target lesions (up to 5), while on study therapy stratified by dose level; Overall response (OR)=CR+PR.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">33</enrollment>
  <condition>Childhood Solid Neoplasm</condition>
  <condition>Recurrent Malignant Solid Neoplasm</condition>
  <condition>Recurrent Primary Central Nervous System Neoplasm</condition>
  <condition>Refractory Malignant Solid Neoplasm</condition>
  <condition>Refractory Primary Central Nervous System Neoplasm</condition>
  <arm_group>
    <arm_group_label>Treatment (nab-rapamycin, temozolomide, irinotecan)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive nanoparticle albumin-bound rapamycin IV over 30 minutes on days 1 and 8 beginning on cycle 1. Patients also receive temozolomide PO and irinotecan hydrochloride PO on days 1-5 beginning on cycle 2. Treatment repeats every 21 days for up to 35 cycles in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Irinotecan Hydrochloride</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Treatment (nab-rapamycin, temozolomide, irinotecan)</arm_group_label>
    <other_name>Campto</other_name>
    <other_name>Camptosar</other_name>
    <other_name>Camptothecin 11</other_name>
    <other_name>Camptothecin-11</other_name>
    <other_name>CPT 11</other_name>
    <other_name>CPT-11</other_name>
    <other_name>Irinomedac</other_name>
    <other_name>Irinotecan Hydrochloride Trihydrate</other_name>
    <other_name>Irinotecan Monohydrochloride Trihydrate</other_name>
    <other_name>U-101440E</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Laboratory Biomarker Analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment (nab-rapamycin, temozolomide, irinotecan)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Pharmacological Study</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment (nab-rapamycin, temozolomide, irinotecan)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sirolimus Albumin-bound Nanoparticles</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (nab-rapamycin, temozolomide, irinotecan)</arm_group_label>
    <other_name>ABI-009</other_name>
    <other_name>Albumin-bound Sirolimus</other_name>
    <other_name>Fyarro</other_name>
    <other_name>Nab-Rapamycin</other_name>
    <other_name>Nab-sirolimus</other_name>
    <other_name>Nanoparticle Albumin-Bound Rapamycin</other_name>
    <other_name>Nanoparticle Albumin-bound Sirolimus</other_name>
    <other_name>Sirolimus Albumin-bound Particles</other_name>
    <other_name>Sirolimus Protein-bound Particles</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Temozolomide</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Treatment (nab-rapamycin, temozolomide, irinotecan)</arm_group_label>
    <other_name>CCRG-81045</other_name>
    <other_name>Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-</other_name>
    <other_name>M &amp; B 39831</other_name>
    <other_name>M and B 39831</other_name>
    <other_name>Methazolastone</other_name>
    <other_name>RP-46161</other_name>
    <other_name>SCH 52365</other_name>
    <other_name>Temcad</other_name>
    <other_name>Temodal</other_name>
    <other_name>Temodar</other_name>
    <other_name>Temomedac</other_name>
    <other_name>TMZ</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients must have a body surface area (BSA) of &gt;= 0.2 m^2 at the time of study&#xD;
             enrollment&#xD;
&#xD;
          -  Patients with recurrent or refractory solid tumors, including CNS tumors, are&#xD;
             eligible; patients must have had histologic verification of malignancy at original&#xD;
             diagnosis or relapse except in patients with intrinsic brain stem tumors, optic&#xD;
             pathway gliomas, or patients with pineal tumors and elevations of cerebrospinal fluid&#xD;
             (CSF) or serum tumor markers including alpha-fetoprotein or beta-human chorionic&#xD;
             gonadotropin (HCG)&#xD;
&#xD;
          -  Patients must have either measurable or evaluable disease&#xD;
&#xD;
          -  Patient's current disease state must be one for which there is no known curative&#xD;
             therapy&#xD;
&#xD;
          -  Karnofsky &gt;= 50% for patients &gt; 16 years of age and Lansky &gt;= 50 for patients =&lt; 16&#xD;
             years of age&#xD;
&#xD;
               -  Note: Neurologic deficits in patients with CNS tumors must have been relatively&#xD;
                  stable for at least 7 days prior to study enrollment; patients who are unable to&#xD;
                  walk because of paralysis, but who are up in a wheelchair, will be considered&#xD;
                  ambulatory for the purpose of assessing the performance score&#xD;
&#xD;
          -  Patients must have fully recovered from the acute toxic effects of all prior&#xD;
             anti-cancer therapy and must meet the following minimum duration from prior&#xD;
             anti-cancer directed therapy prior to enrollment; if after the required timeframe, the&#xD;
             numerical eligibility criteria are met, e.g. blood count criteria, the patient is&#xD;
             considered to have recovered adequately&#xD;
&#xD;
          -  Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive; the&#xD;
             duration of this interval must be discussed with the study chair and the&#xD;
             study-assigned research coordinator prior to enrollment&#xD;
&#xD;
               -  &gt;= 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy (42&#xD;
                  days if prior nitrosourea)&#xD;
&#xD;
          -  Anti-cancer agents not known to be myelosuppressive (e.g. not associated with reduced&#xD;
             platelet or absolute neutrophil count [ANC] counts): &gt;= 7 days after the last dose of&#xD;
             agent; the duration of this interval must be discussed with the study chair and the&#xD;
             study-assigned research coordinator prior to enrollment&#xD;
&#xD;
          -  Antibodies: &gt;= 21 days must have elapsed from infusion of last dose of antibody, and&#xD;
             toxicity related to prior antibody therapy must be recovered to grade =&lt; 1&#xD;
&#xD;
          -  Corticosteroids: If used to modify immune adverse events related to prior therapy, &gt;=&#xD;
             14 days must have elapsed since last dose of corticosteroid&#xD;
&#xD;
          -  Hematopoietic growth factors: &gt;= 14 days after the last dose of a long-acting growth&#xD;
             factor (e.g. pegfilgrastim) or 7 days for short-acting growth factor; for agents that&#xD;
             have known adverse events occurring beyond 7 days after administration, this period&#xD;
             must be extended beyond the time during which adverse events are known to occur; the&#xD;
             duration of this interval must be discussed with the study chair and the&#xD;
             study-assigned research coordinator&#xD;
&#xD;
          -  Interleukins, interferons and cytokines (other than hematopoietic growth factors): &gt;=&#xD;
             21 days after the completion of interleukins, interferon or cytokines (other than&#xD;
             hematopoietic growth factors)&#xD;
&#xD;
          -  Stem cell infusions (with or without total body irradiation [TBI]):&#xD;
&#xD;
               -  Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell&#xD;
                  infusion including donor lymphocyte infusion (DLI) or boost infusion: &gt;= 84 days&#xD;
                  after infusion, and no evidence of graft-versus-host disease (GVHD)&#xD;
&#xD;
               -  Autologous stem cell infusion including boost infusion: &gt;= 42 days&#xD;
&#xD;
          -  Cellular therapy: &gt;= 42 days after the completion of any type of cellular therapy&#xD;
             (e.g. modified T cells, natural killer [NK] cells, dendritic cells, etc.)&#xD;
&#xD;
          -  X ray (XRT)/external beam irradiation including protons: &gt;= 14 days after local XRT;&#xD;
             &gt;= 150 days after TBI, craniospinal XRT or if radiation to &gt;= 50% of the pelvis; &gt;= 42&#xD;
             days if other substantial bone marrow (BM) radiation&#xD;
&#xD;
          -  Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131 iodine&#xD;
             metaiodobenzylguanidine [131I-MIBG]): &gt;= 42 days after systemically administered&#xD;
             radiopharmaceutical therapy&#xD;
&#xD;
          -  Irinotecan, temozolomide and mammalian target of rapamycin (mTOR) inhibitor exposure:&#xD;
&#xD;
               -  Patients who have received prior single agent therapy with irinotecan,&#xD;
                  temozolomide, or an mTOR inhibitor, excluding ABI-009, are eligible&#xD;
&#xD;
               -  Patients who have received prior therapy with ABI-009 are not eligible&#xD;
&#xD;
               -  Patients who have previously received irinotecan and temozolomide in combination&#xD;
                  without progressive disease while on therapy are eligible&#xD;
&#xD;
               -  Patients who have previously received irinotecan and temozolomide in combination&#xD;
                  and had significant toxicity with these two drugs are not eligible&#xD;
&#xD;
               -  Patients who have received prior therapy with all three agents in combination&#xD;
                  (i.e. irinotecan, temozolomide, and an mTOR inhibitor) are not eligible&#xD;
&#xD;
          -  Adequate Bone Marrow Function Defined as:&#xD;
&#xD;
          -  For patients with solid tumors without known bone marrow involvement (no older than 7&#xD;
             days at the start of therapy):&#xD;
&#xD;
               -  Peripheral absolute neutrophil count (ANC) &gt;= 1000/mm^3&#xD;
&#xD;
               -  Platelet count &gt;= 100,000/mm^3 (transfusion independent, defined as not receiving&#xD;
                  platelet transfusions for at least 7 days prior to enrollment)&#xD;
&#xD;
               -  Hemoglobin &gt;= 8.0 g/dl at baseline (may receive red blood cell [RBC]&#xD;
                  transfusions)&#xD;
&#xD;
          -  Creatinine clearance or radioisotope glomerular filtration rate (GFR) &gt;= 70&#xD;
             ml/min/1.73 m^2 or a serum creatinine based on age/gender as follows (no older than 7&#xD;
             days at the start of therapy):&#xD;
&#xD;
               -  Age: maximum serum creatinine (mg/dL)&#xD;
&#xD;
               -  1 to &lt; 2 years: 0.6 (male and female)&#xD;
&#xD;
               -  2 to &lt; 6 years: 0.8 (male and female)&#xD;
&#xD;
               -  6 to &lt; 10 years: 1 (male and female)&#xD;
&#xD;
               -  10 to &lt; 13 years: 1.2 (male and female)&#xD;
&#xD;
               -  13 to &lt; 16 years: 1.5 (male), 1.4 (female)&#xD;
&#xD;
               -  &gt;= 16 years: 1.7 (male), 1.4 (female)&#xD;
&#xD;
          -  Bilirubin (sum of conjugated + unconjugated) =&lt; 1.5 x upper limit of normal (ULN) for&#xD;
             age (no older than 7 days at the start of therapy)&#xD;
&#xD;
          -  Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =&lt; 3 x&#xD;
             ULN = 135 U/L; for the purpose of this study, the ULN for SGPT is 45 U/L (no older&#xD;
             than 7 days at the start of therapy)&#xD;
&#xD;
          -  Serum albumin &gt;= 2 g/dL (no older than 7 days at the start of therapy)&#xD;
&#xD;
          -  Pulse oximetry &gt; 94% on room air if there is clinical indication for determination&#xD;
             (e.g. dyspnea at rest)&#xD;
&#xD;
          -  Patients with seizure disorder may be enrolled if on non-enzyme inducing&#xD;
             anticonvulsants and well controlled&#xD;
&#xD;
          -  Nervous system disorders (National Cancer Institute Common Terminology Criteria for&#xD;
             Adverse Events [NCI CTCAE] version 5.0) resulting from prior therapy must be =&lt; grade&#xD;
             2 with the exception of decreased tendon reflex (DTR); any grade of DTR is eligible&#xD;
&#xD;
          -  Serum triglyceride level =&lt; 300 mg/dL (no older than 7 days at the start of therapy)&#xD;
&#xD;
          -  Serum total cholesterol level =&lt; 300 mg/dL (no older than 7 days at the start of&#xD;
             therapy)&#xD;
&#xD;
          -  Random or fasting blood glucose =&lt; the upper normal limits for age; if the initial&#xD;
             blood glucose is a random sample that is outside of the normal limits, then follow-up&#xD;
             fasting blood glucose can be obtained and must be =&lt; the upper normal limits for age&#xD;
             (no older than 7 days at the start of therapy)&#xD;
&#xD;
          -  International normalized ratio (INR) =&lt; 1.5 (no older than 7 days at the start of&#xD;
             therapy)&#xD;
&#xD;
          -  Not currently receiving anticoagulation therapy&#xD;
&#xD;
          -  All patients and/or their parents or legally authorized representatives must sign a&#xD;
             written informed consent; assent, when appropriate, will be obtained according to&#xD;
             institutional guidelines&#xD;
&#xD;
          -  Tissue blocks or slides must be sent for all patients; if tissue blocks or slides are&#xD;
             unavailable, the study chair must be notified prior to enrollment&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant or breast-feeding women will not be entered on this study due to risks of&#xD;
             fetal and teratogenic adverse events as seen in animal/human studies; pregnancy tests&#xD;
             must be obtained in girls who are post-menarchal; males or females of reproductive&#xD;
             potential may not participate unless they have agreed to use an effective&#xD;
             contraceptive method both during and for 6 months after participation in this study;&#xD;
             abstinence is an acceptable method of contraception&#xD;
&#xD;
          -  Patients receiving corticosteroids must have been on a stable or decreasing dose of&#xD;
             corticosteroid for at least 7 days prior to enrollment; if used to modify immune&#xD;
             adverse events related to prior therapy, &gt;= 14 days must have elapsed since last dose&#xD;
             of corticosteroid&#xD;
&#xD;
          -  Patients who are currently receiving another investigational drug are not eligible&#xD;
&#xD;
          -  Patients who are currently receiving other anti-cancer agents are not eligible&#xD;
&#xD;
          -  Patients who are receiving cyclosporine, tacrolimus or other agents to prevent&#xD;
             graft-versus-host disease post bone marrow transplant are not eligible for this trial&#xD;
&#xD;
          -  Patients must not have received enzyme-inducing anticonvulsants for at least 7 days&#xD;
             prior to enrollment&#xD;
&#xD;
          -  Patients who are currently receiving therapeutic anticoagulants (including aspirin,&#xD;
             low molecular weight heparin, and others) are not eligible&#xD;
&#xD;
          -  Patients must not be receiving any strong CYP3A4 or P-glycoprotein (P-gp) inducers or&#xD;
             inhibitors within 7 days prior to enrollment; moderate inducers or inhibitors of&#xD;
             CYP3A4 and P-gp should also be avoided during ABI-009 treatment, if possible&#xD;
&#xD;
          -  Patients with interstitial lung disease and/or pneumonitis are not eligible&#xD;
&#xD;
          -  Patients with a history of allergic reactions attributed to compounds of similar&#xD;
             composition, including macrolide and ketolide antibiotics, temsirolimus/other mTOR&#xD;
             inhibitors, temozolomide or irinotecan are not eligible&#xD;
&#xD;
          -  Patients with hypersensitivity to albumin are not eligible&#xD;
&#xD;
          -  Patients who have had or are planning to have the following invasive procedures are&#xD;
             not eligible:&#xD;
&#xD;
               -  Major surgical procedure, laparoscopic procedure, open biopsy or significant&#xD;
                  traumatic injury within 28 days prior to enrollment&#xD;
&#xD;
               -  Subcutaneous port placement or central line placement is not considered major&#xD;
                  surgery; external central lines must be placed at least 3 days prior to&#xD;
                  enrollment and subcutaneous ports must be placed at least 7 days prior to&#xD;
                  enrollment&#xD;
&#xD;
               -  Core biopsy within 7 days prior to enrollment&#xD;
&#xD;
               -  Fine needle aspirate within 7 days prior to enrollment&#xD;
&#xD;
               -  NOTE: For purposes of this study, bone marrow aspirate and biopsy are not&#xD;
                  considered surgical procedures and therefore are permitted within 14 days prior&#xD;
                  to start of protocol therapy&#xD;
&#xD;
          -  Patients with current deep vein thrombosis or deep vein thrombosis within the past 6&#xD;
             months are not eligible&#xD;
&#xD;
          -  Patients with a history of, or current grade 4 depression are not eligible&#xD;
&#xD;
          -  Patients who have an uncontrolled infection are not eligible&#xD;
&#xD;
          -  Patients who have received a prior solid organ transplantation are not eligible&#xD;
&#xD;
          -  Patients who have known bone marrow involvement are not eligible&#xD;
&#xD;
          -  Patients who in the opinion of the investigator may not be able to comply with the&#xD;
             safety monitoring requirements of the study are not eligible&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>12 Months</minimum_age>
    <maximum_age>21 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Stuart L Cramer</last_name>
    <role>Principal Investigator</role>
    <affiliation>COG Phase I Consortium</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Children's Hospital of Alabama</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35233</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital Los Angeles</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90027</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital of Orange County</name>
      <address>
        <city>Orange</city>
        <state>California</state>
        <zip>92868</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UCSF Medical Center-Mission Bay</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94158</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital Colorado</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's National Medical Center</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Healthcare of Atlanta - Egleston</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lurie Children's Hospital-Chicago</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Riley Hospital for Children</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dana-Farber Cancer Institute</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>C S Mott Children's Hospital</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Minnesota/Masonic Cancer Center</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55455</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington University School of Medicine</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cincinnati Children's Hospital Medical Center</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital of Philadelphia</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital of Pittsburgh of UPMC</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15224</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Prisma Health Richland Hospital</name>
      <address>
        <city>Columbia</city>
        <state>South Carolina</state>
        <zip>29203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Jude Children's Research Hospital</name>
      <address>
        <city>Memphis</city>
        <state>Tennessee</state>
        <zip>38105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seattle Children's Hospital</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>November 15, 2016</study_first_submitted>
  <study_first_submitted_qc>November 23, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 29, 2016</study_first_posted>
  <results_first_submitted>February 16, 2023</results_first_submitted>
  <results_first_submitted_qc>March 29, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">March 30, 2023</results_first_posted>
  <last_update_submitted>April 24, 2023</last_update_submitted>
  <last_update_submitted_qc>April 24, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 26, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</mesh_term>
    <mesh_term>Nervous System Neoplasms</mesh_term>
    <mesh_term>Central Nervous System Neoplasms</mesh_term>
    <mesh_term>Recurrence</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sirolimus</mesh_term>
    <mesh_term>Irinotecan</mesh_term>
    <mesh_term>Camptothecin</mesh_term>
    <mesh_term>Temozolomide</mesh_term>
    <mesh_term>Temsirolimus</mesh_term>
    <mesh_term>MTOR Inhibitors</mesh_term>
  </intervention_browse>
  <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>June 19, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/82/NCT02975882/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Stratum Cohort With Dose Level 1</title>
          <description>35 mg/m^2 ABI-009 + 90 mg/m^2 Irinotecan + 125 mg/m^2 Temozolomide</description>
        </group>
        <group group_id="P2">
          <title>Stratum Cohort With Dose Level -1</title>
          <description>20 mg/m^2 ABI-009 + 90 mg/m^2 Irinotecan + 125 mg/m^2 Temozolomide</description>
        </group>
        <group group_id="P3">
          <title>Stratum Cohort With Dose Level -2</title>
          <description>15 mg/m^2 ABI-009 + 90 mg/m^2 Irinotecan + 125 mg/m^2 Temozolomide</description>
        </group>
        <group group_id="P4">
          <title>PK Cohort With Dose Level -2</title>
          <description>15 mg/m^2 ABI-009 + 90 mg/m^2 Irinotecan + 125 mg/m^2 Temozolomide</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="13"/>
                <participants group_id="P3" count="9"/>
                <participants group_id="P4" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="13"/>
                <participants group_id="P3" count="9"/>
                <participants group_id="P4" count="6"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</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_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="7"/>
                <participants group_id="P3" count="4"/>
                <participants group_id="P4" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="4"/>
                <participants group_id="P4" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Ineligible</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_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Patients must have a body surface area (BSA) of &gt;= 0.2 m^2 at the time of study enrollment: Karnofsky &gt;= 50% for patients &gt; 16 years of age and Lansky &gt;= 50 for patients =&lt; 16 years of age.</population>
      <group_list>
        <group group_id="B1">
          <title>Stratum Cohort With Dose Level 1</title>
          <description>35 mg/m^2 ABI-009 + 90 mg/m^2 Irinotecan + 125 mg/m^2 Temozolomide</description>
        </group>
        <group group_id="B2">
          <title>Stratum Cohort With Dose Level -1</title>
          <description>20 mg/m^2 ABI-009 + 90 mg/m^2 Irinotecan + 125 mg/m^2 Temozolomide</description>
        </group>
        <group group_id="B3">
          <title>Stratum Cohort With Dose Level -2</title>
          <description>15 mg/m^2 ABI-009 + 90 mg/m^2 Irinotecan + 125 mg/m^2 Temozolomide</description>
        </group>
        <group group_id="B4">
          <title>PK Cohort With Dose Level -2</title>
          <description>15 mg/m^2 ABI-009 + 90 mg/m^2 Irinotecan + 125 mg/m^2 Temozolomide</description>
        </group>
        <group group_id="B5">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="5"/>
            <count group_id="B2" value="13"/>
            <count group_id="B3" value="9"/>
            <count group_id="B4" value="6"/>
            <count group_id="B5" value="33"/>
          </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="4"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="8"/>
                    <measurement group_id="B4" value="6"/>
                    <measurement group_id="B5" value="28"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 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_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="11" lower_limit="7" upper_limit="20"/>
                    <measurement group_id="B2" value="13" lower_limit="3" upper_limit="20"/>
                    <measurement group_id="B3" value="12" lower_limit="1" upper_limit="21"/>
                    <measurement group_id="B4" value="8" lower_limit="2" upper_limit="16"/>
                    <measurement group_id="B5" value="12" lower_limit="1" upper_limit="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="4"/>
                    <measurement group_id="B5" value="23"/>
                  </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="2"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="8"/>
                    <measurement group_id="B4" value="5"/>
                    <measurement group_id="B5" value="28"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</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="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_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="3"/>
                    <measurement group_id="B5" value="18"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</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="1"/>
                    <measurement group_id="B5" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Patients With Cycle 1 and 2 Dose Limiting Toxicities Attributable to Nanoparticle Albumin-bound Rapamycin</title>
        <description>Number of patients with cycle 1 and 2 dose limiting toxicities possibly, probably, or definitely attributable with nanoparticle albumin-bound rapamycin stratified by dose level.</description>
        <time_frame>Up to 42 days</time_frame>
        <population>All DLT evaluable Patients</population>
        <group_list>
          <group group_id="O1">
            <title>Stratum Cohort With Dose Level 1</title>
            <description>35 mg/m^2 ABI-009 + 90 mg/m^2 Irinotecan + 125 mg/m^2 Temozolomide</description>
          </group>
          <group group_id="O2">
            <title>Stratum Cohort With Dose Level -1</title>
            <description>20 mg/m^2 ABI-009 + 90 mg/m^2 Irinotecan + 125 mg/m^2 Temozolomide</description>
          </group>
          <group group_id="O3">
            <title>Stratum Cohort With Dose Level -2</title>
            <description>15 mg/m^2 ABI-009 + 90 mg/m^2 Irinotecan + 125 mg/m^2 Temozolomide</description>
          </group>
          <group group_id="O4">
            <title>PK Cohort With Dose Level -2</title>
            <description>15 mg/m^2 ABI-009 + 90 mg/m^2 Irinotecan + 125 mg/m^2 Temozolomide</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients With Cycle 1 and 2 Dose Limiting Toxicities Attributable to Nanoparticle Albumin-bound Rapamycin</title>
          <description>Number of patients with cycle 1 and 2 dose limiting toxicities possibly, probably, or definitely attributable with nanoparticle albumin-bound rapamycin stratified by dose level.</description>
          <population>All DLT evaluable Patients</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="5"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Patients With Adverse Events</title>
        <description>The number of patients with adverse events that are at least possibly attributable to nanoparticle albumin-bound rapamycin stratified by dose level.</description>
        <time_frame>Up to 24 months</time_frame>
        <population>All Eligible Patients</population>
        <group_list>
          <group group_id="O1">
            <title>Stratum Cohort With Dose Level 1</title>
            <description>35 mg/m^2 ABI-009 + 90 mg/m^2 Irinotecan + 125 mg/m^2 Temozolomide</description>
          </group>
          <group group_id="O2">
            <title>Stratum Cohort With Dose Level -1</title>
            <description>20 mg/m^2 ABI-009 + 90 mg/m^2 Irinotecan + 125 mg/m^2 Temozolomide</description>
          </group>
          <group group_id="O3">
            <title>Stratum Cohort With Dose Level -2</title>
            <description>15 mg/m^2 ABI-009 + 90 mg/m^2 Irinotecan + 125 mg/m^2 Temozolomide</description>
          </group>
          <group group_id="O4">
            <title>PK Cohort With Dose Level -2</title>
            <description>15 mg/m^2 ABI-009 + 90 mg/m^2 Irinotecan + 125 mg/m^2 Temozolomide</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients With Adverse Events</title>
          <description>The number of patients with adverse events that are at least possibly attributable to nanoparticle albumin-bound rapamycin stratified by dose level.</description>
          <population>All Eligible Patients</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="5"/>
                <count group_id="O2" value="12"/>
                <count group_id="O3" value="9"/>
                <count group_id="O4" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="12"/>
                    <measurement group_id="O3" value="8"/>
                    <measurement group_id="O4" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Area Under the Serum of Nanoparticle Albumin-bound Rapamycin Concentration Curve</title>
        <description>Median with minimum and maximum values of the area under the drug concentration over time curve stratified by dose level.</description>
        <time_frame>Days 1, 2, 3, 4, and 8</time_frame>
        <population>All Eligible Patients</population>
        <group_list>
          <group group_id="O1">
            <title>Stratum Cohort With Dose Level 1</title>
            <description>35 mg/m^2 ABI-009 + 90 mg/m^2 Irinotecan + 125 mg/m^2 Temozolomide</description>
          </group>
          <group group_id="O2">
            <title>Stratum Cohort With Dose Level -1</title>
            <description>20 mg/m^2 ABI-009 + 90 mg/m^2 Irinotecan + 125 mg/m^2 Temozolomide</description>
          </group>
          <group group_id="O3">
            <title>Stratum Cohort With Dose Level -2</title>
            <description>15 mg/m^2 ABI-009 + 90 mg/m^2 Irinotecan + 125 mg/m^2 Temozolomide</description>
          </group>
          <group group_id="O4">
            <title>PK Cohort With Dose Level -2</title>
            <description>15 mg/m^2 ABI-009 + 90 mg/m^2 Irinotecan + 125 mg/m^2 Temozolomide</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Serum of Nanoparticle Albumin-bound Rapamycin Concentration Curve</title>
          <description>Median with minimum and maximum values of the area under the drug concentration over time curve stratified by dose level.</description>
          <population>All Eligible Patients</population>
          <units>hr*ng/mL</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="12"/>
                <count group_id="O3" value="9"/>
                <count group_id="O4" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13654" lower_limit="8610.0" upper_limit="19617.0"/>
                    <measurement group_id="O2" value="9532" lower_limit="5352.0" upper_limit="18625.0"/>
                    <measurement group_id="O3" value="8666" lower_limit="5074.0" upper_limit="12224.0"/>
                    <measurement group_id="O4" value="7988.5" lower_limit="4826.0" upper_limit="11366.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Patients With Antitumor Activity of Nanoparticle Albumin-bound Rapamycin</title>
        <description>The number of response-evaluable patients with best overall response of complete response (CR), disappearance of all target lesions; or partial response (PR), &gt;=50% decrease in the sum of the products of the two perpendicular diameters of all target lesions (up to 5), while on study therapy stratified by dose level; Overall response (OR)=CR+PR.</description>
        <time_frame>Up to 24 months</time_frame>
        <population>All Eligible Patients</population>
        <group_list>
          <group group_id="O1">
            <title>Stratum Cohort With Dose Level 1</title>
            <description>35 mg/m^2 ABI-009 + 90 mg/m^2 Irinotecan + 125 mg/m^2 Temozolomide</description>
          </group>
          <group group_id="O2">
            <title>Stratum Cohort With Dose Level -1</title>
            <description>20 mg/m^2 ABI-009 + 90 mg/m^2 Irinotecan + 125 mg/m^2 Temozolomide</description>
          </group>
          <group group_id="O3">
            <title>Stratum Cohort With Dose Level -2</title>
            <description>15 mg/m^2 ABI-009 + 90 mg/m^2 Irinotecan + 125 mg/m^2 Temozolomide</description>
          </group>
          <group group_id="O4">
            <title>PK Cohort With Dose Level -2</title>
            <description>15 mg/m^2 ABI-009 + 90 mg/m^2 Irinotecan + 125 mg/m^2 Temozolomide</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients With Antitumor Activity of Nanoparticle Albumin-bound Rapamycin</title>
          <description>The number of response-evaluable patients with best overall response of complete response (CR), disappearance of all target lesions; or partial response (PR), &gt;=50% decrease in the sum of the products of the two perpendicular diameters of all target lesions (up to 5), while on study therapy stratified by dose level; Overall response (OR)=CR+PR.</description>
          <population>All Eligible Patients</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="5"/>
                <count group_id="O2" value="12"/>
                <count group_id="O3" value="9"/>
                <count group_id="O4" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Up to 5 years</time_frame>
      <desc>Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the &quot;AE Other&quot; table. Ineligible patients are excluded from reporting of adverse events. All-Cause Mortality includes all deaths collected on the study.</desc>
      <group_list>
        <group group_id="E1">
          <title>Stratum Cohort With Dose Level 1</title>
          <description>35 mg/m^2 ABI-009 + 90 mg/m^2 Irinotecan + 125 mg/m^2 Temozolomide</description>
        </group>
        <group group_id="E2">
          <title>Stratum Cohort With Dose Level -1</title>
          <description>20 mg/m^2 ABI-009 + 90 mg/m^2 Irinotecan + 125 mg/m^2 Temozolomide</description>
        </group>
        <group group_id="E3">
          <title>Stratum Cohort With Dose Level -2</title>
          <description>15 mg/m^2 ABI-009 + 90 mg/m^2 Irinotecan + 125 mg/m^2 Temozolomide</description>
        </group>
        <group group_id="E4">
          <title>PK Cohort With Dose Level -2</title>
          <description>15 mg/m^2 ABI-009 + 90 mg/m^2 Irinotecan + 125 mg/m^2 Temozolomide</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="8" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="5" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Pericardial effusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Pericardial tamponade</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Sinus tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Hearing impaired</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Delayed puberty</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Duodenal hemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Duodenal ulcer</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Gastrointestinal disorders - Other, Enteritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Mucositis oral</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Enterocolitis infectious</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Gum infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Skin infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Upper respiratory infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Alkaline phosphatase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Urine output decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Weight gain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Weight loss</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>White blood cell decreased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Acidosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hypophosphatemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Obesity</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Bone pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Chest wall pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Joint range of motion decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Muscle weakness lower limb</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Tumor pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Depressed level of consciousness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Intracranial hemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Paresthesia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Cystitis noninfective</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Proteinuria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Wheezing</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Skin ulceration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Surgical and medical procedures - Other, RENAL STENT PLACEMENT</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Thromboembolic event</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="9" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="6" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="8" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="5" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Palpitations</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Pericardial effusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Sinus bradycardia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Sinus tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>External ear pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Endocrine disorders - Other,</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hypothyroidism</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Blurred vision</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Eye disorders - Other, Double vision</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Eye disorders - Other, Left eye itching</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Eye disorders - Other, RIGHT ESOTROPIA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Eye disorders - Other, visual disturbance</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Eye pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Flashing lights</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Periorbital edema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal distension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Anal hemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Ascites</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Bloating</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Dental caries</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Duodenal obstruction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Esophagitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Fecal incontinence</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Flatulence</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Gastric hemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Gastroesophageal reflux disease</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Gastrointestinal disorders - Other, Lip Lesion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Gastrointestinal disorders - Other, MOTILITY</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Gastrointestinal disorders - Other, hematochezia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Gingival pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Mucositis oral</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Oral dysesthesia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Oral pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Rectal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Edema face</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Edema limbs</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Gait disturbance</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>General disorders and administration site conditions - Other,</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>General disorders and administration site conditions - Other, LEFT SIDE HEMIPARESIS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Localized edema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Neck edema</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Hepatobiliary disorders - Other,</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Immune system disorders - Other, SEASONAL ALLERGIES</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Conjunctivitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Enterocolitis infectious</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Infections and infestations - Other,</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Infections and infestations - Other, C. DIFF</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Infections and infestations - Other, COVID-19</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Mucosal infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Otitis media</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Papulopustular rash</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Upper respiratory infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Bruising</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Activated partial thromboplastin time prolonged</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Alkaline phosphatase increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Cholesterol high</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="8" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Creatinine increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hemoglobin increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>INR increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Investigations - Other,</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Investigations - Other, AFP Tumor Marker Increase</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Investigations - Other, BICARBONATE &lt; LLN</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Investigations - Other, C-reactive protein increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Investigations - Other, DECREASED CARBON DIOXIDE</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Investigations - Other, HDL Cholesterol decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Investigations - Other, HYPOCHLOREMIA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Investigations - Other, Neutrophil count increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Lipase increased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Serum amylase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Weight gain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Weight loss</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>White blood cell decreased</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="9" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="5" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hypercalcemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="8" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hyperkalemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hypermagnesemia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hypernatremia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hypertriglyceridemia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hypoalbuminemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hypocalcemia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hypoglycemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hypomagnesemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hypophosphatemia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Metabolism and nutrition disorders - Other, HYPOCHLOREMIA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Metabolism and nutrition disorders - Other, Vitamin D deficiency</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Bone pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Buttock pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Chest wall pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Flank pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Generalized muscle weakness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Joint range of motion decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Muscle weakness lower limb</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Muscle weakness upper limb</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Musculoskeletal and connective tissue disorder - Other,</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Musculoskeletal and connective tissue disorder - Other, toe pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Neck pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Osteoporosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Tumor pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Ataxia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Central nervous system necrosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Cognitive disturbance</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Dysarthria</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Facial nerve disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hydrocephalus</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hypersomnia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Lethargy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Memory impairment</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Muscle weakness right-sided</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Nervous system disorders - Other, Disconjugated gaze</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Oculomotor nerve disorder</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Paresthesia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Peripheral motor neuropathy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Peripheral sensory neuropathy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Phantom pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Seizure</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Spasticity</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Tremor</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Confusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Delirium</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Irritability</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Restlessness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Chronic kidney disease</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hematuria</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hemoglobinuria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Proteinuria</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Renal and urinary disorders - Other,</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Urinary frequency</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Urinary incontinence</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Urinary retention</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Urinary tract pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Urinary urgency</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Genital edema</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Pelvic pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Reproductive system and breast disorders - Other,</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </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" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Atelectasis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Bronchial obstruction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hoarseness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Laryngeal hemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Pneumonitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Pneumothorax</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Postnasal drip</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Productive cough</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Pulmonary edema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Respiratory, thoracic and mediastinal disorders - Other, RHINORRHEA</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Respiratory, thoracic and mediastinal disorders - Other, TACHYPNEA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Respiratory, thoracic and mediastinal disorders - Other, Tachypnea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Respiratory, thoracic and mediastinal disorders - Other, Tachypnea and Respiratory distress</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Respiratory, thoracic and mediastinal disorders - Other, tachypnea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Sneezing</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Sore throat</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Wheezing</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hyperhidrosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Pain of skin</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Rash acneiform</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Skin and subcutaneous tissue disorders - Other, ATOPIC DERMATITIS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Skin and subcutaneous tissue disorders - Other, Diaper rash</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Skin and subcutaneous tissue disorders - Other, Skin erythema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Skin and subcutaneous tissue disorders - Other, bug bite</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Skin and subcutaneous tissue disorders - Other, forehead abrasion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Flushing</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hot flashes</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Phlebitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>Must obtain prior Sponsor approval</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Results Reporting Coordinator</name_or_title>
      <organization>Children's Oncology Group</organization>
      <phone>16264470064</phone>
      <email>resultsreportingcoordinator@childrensoncologygroup.org</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/NCT02975882
org study id: ADVL1514
secondary id: NCI-2016-01412
secondary id: ADVL1514
secondary id: ADVL1514
secondary id: ADVL1514
secondary id: UM1CA097452
nct id: NCT02975882
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This phase I trial studies the side effects and best dose of nanoparticle albumin-bound
      rapamycin when given together with temozolomide and irinotecan hydrochloride in treating
      pediatric patients with solid tumors that have come back after treatment and a period of time
      during which the tumor could not be detected or has not responded to treatment. Nanoparticle
      albumin-bound rapamycin may stop the growth of tumor cells by blocking some of the enzymes
      needed for cell growth. Chemotherapy drugs, such as temozolomide and irinotecan
      hydrochloride, work in different ways to stop the growth of tumor cells, either by killing
      the cells, by stopping them from dividing, or by stopping them from spreading. Giving
      nanoparticle albumin-bound rapamycin, temozolomide, and irinotecan hydrochloride may cause
      the cancer to stop growing or shrink for a period of time and may lessen the symptoms that
      are caused by the cancer.
PRIMARY OBJECTIVES:

      I. To estimate the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of
      nanoparticle albumin-bound rapamycin (ABI-009) administered as an intravenous infusion over
      30 minutes on days 1 and 8 of a 21-day cycle, in combination with temozolomide and irinotecan
      hydrochloride (irinotecan) (administered on days 1-5) in pediatric patients with recurrent or
      refractory solid tumors, including central nervous system (CNS) tumors.

      II. To define and describe the toxicities of single-agent ABI-009 administered as an
      intravenous infusion over 30 minutes on days 1 and 8 of a 21-day cycle in pediatric patients
      with recurrent or refractory solid tumors, including CNS tumors.

      III. To define and describe the toxicities of ABI-009 administered as an intravenous infusion
      over 30 minutes on days 1 and 8 of a 21-day cycle in combination with temozolomide and
      irinotecan (administered on days 1-5) in pediatric patients with recurrent or refractory
      solid tumors, including CNS tumors.

      IV. To characterize the pharmacokinetics of ABI-009 in pediatric patients with recurrent or
      refractory solid tumors, including CNS tumors.

      SECONDARY OBJECTIVE:

      I. To preliminarily define the antitumor activity of ABI-009 in combination with temozolomide
      and irinotecan within the confines of a phase 1 study.

      EXPLORATORY OBJECTIVE:

      I. To assess the biologic activity of ABI-009 by examining S6K1 and 4E-BP1 expression status
      in archival tumor tissue from solid tumor pediatric patients using immunohistochemistry.

      OUTLINE: This is a dose-escalation study of nanoparticle albumin-bound rapamycin.

      Patients receive nanoparticle albumin-bound rapamycin intravenously (IV) over 30 minutes on
      days 1 and 8 beginning on cycle 1. Patients also receive temozolomide orally (PO) and
      irinotecan hydrochloride PO on days 1-5 beginning on cycle 2. Treatment repeats every 21 days
      for up to 35 cycles in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up periodically.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Patients With Cycle 1 and 2 Dose Limiting Toxicities Attributable to Nanoparticle Albumin-bound Rapamycin
time frame: Up to 42 days
description: Number of patients with cycle 1 and 2 dose limiting toxicities possibly, probably, or definitely attributable with nanoparticle albumin-bound rapamycin stratified by dose level.
measure: Number of Patients With Adverse Events
time frame: Up to 24 months
description: The number of patients with adverse events that are at least possibly attributable to nanoparticle albumin-bound rapamycin stratified by dose level.
measure: Area Under the Serum of Nanoparticle Albumin-bound Rapamycin Concentration Curve
time frame: Days 1, 2, 3, 4, and 8
description: Median with minimum and maximum values of the area under the drug concentration over time curve stratified by dose level.
measure: Number of Patients With Antitumor Activity of Nanoparticle Albumin-bound Rapamycin
time frame: Up to 24 months
description: The number of response-evaluable patients with best overall response of complete response (CR), disappearance of all target lesions; or partial response (PR), >=50% decrease in the sum of the products of the two perpendicular diameters of all target lesions (up to 5), while on study therapy stratified by dose level; Overall response (OR)=CR+PR.
arm group label: Treatment (nab-rapamycin, temozolomide, irinotecan)
arm group type: Experimental
description: Patients receive nanoparticle albumin-bound rapamycin IV over 30 minutes on days 1 and 8 beginning on cycle 1. Patients also receive temozolomide PO and irinotecan hydrochloride PO on days 1-5 beginning on cycle 2. Treatment repeats every 21 days for up to 35 cycles in the absence of disease progression or unacceptable toxicity.
intervention type: Drug
intervention name: Irinotecan Hydrochloride
description: Given PO
arm group label: Treatment (nab-rapamycin, temozolomide, irinotecan)
other name: Campto
other name: Camptosar
other name: Camptothecin 11
other name: Camptothecin-11
other name: CPT 11
other name: CPT-11
other name: Irinomedac
other name: Irinotecan Hydrochloride Trihydrate
other name: Irinotecan Monohydrochloride Trihydrate
other name: U-101440E
intervention type: Other
intervention name: Laboratory Biomarker Analysis
description: Correlative studies
arm group label: Treatment (nab-rapamycin, temozolomide, irinotecan)
intervention type: Other
intervention name: Pharmacological Study
description: Correlative studies
arm group label: Treatment (nab-rapamycin, temozolomide, irinotecan)
intervention type: Drug
intervention name: Sirolimus Albumin-bound Nanoparticles
description: Given IV
arm group label: Treatment (nab-rapamycin, temozolomide, irinotecan)
other name: ABI-009
other name: Albumin-bound Sirolimus
other name: Fyarro
other name: Nab-Rapamycin
other name: Nab-sirolimus
other name: Nanoparticle Albumin-Bound Rapamycin
other name: Nanoparticle Albumin-bound Sirolimus
other name: Sirolimus Albumin-bound Particles
other name: Sirolimus Protein-bound Particles
intervention type: Drug
intervention name: Temozolomide
description: Given PO
arm group label: Treatment (nab-rapamycin, temozolomide, irinotecan)
other name: CCRG-81045
other name: Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-
other name: M & B 39831
other name: M and B 39831
other name: Methazolastone
other name: RP-46161
other name: SCH 52365
other name: Temcad
other name: Temodal
other name: Temodar
other name: Temomedac
other name: TMZ
criteria: 
gender: All
minimum age: 12 Months
maximum age: 21 Years
healthy volunteers: No
last name: Stuart L Cramer
role: Principal Investigator
affiliation: COG Phase I Consortium
facility: 
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country: United States
responsible party type: Sponsor
mesh term: Neoplasms
mesh term: Nervous System Neoplasms
mesh term: Central Nervous System Neoplasms
mesh term: Recurrence
mesh term: Sirolimus
mesh term: Irinotecan
mesh term: Camptothecin
mesh term: Temozolomide
mesh term: Temsirolimus
mesh term: MTOR Inhibitors
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 