<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/NCT03245151</url>
  </required_header>
  <id_info>
    <org_study_id>E7080-A001-216</org_study_id>
    <nct_id>NCT03245151</nct_id>
  </id_info>
  <brief_title>Study of Lenvatinib in Combination With Everolimus in Recurrent and Refractory Pediatric Solid Tumors, Including Central Nervous System Tumors</brief_title>
  <official_title>A Phase 1/2 Study of Lenvatinib in Combination With Everolimus in Recurrent and Refractory Pediatric Solid Tumors, Including CNS Tumors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Eisai Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Merck Sharp &amp; Dohme LLC</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Eisai Inc.</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>
      Phase 1 of this study, utilizing a rolling 6 design, will be conducted to determine a maximum&#xD;
      tolerated dose (MTD) and recommended Phase 2 dose (RP2D), and to describe the toxicities of&#xD;
      lenvatinib administered in combination with everolimus once daily to pediatric participants&#xD;
      with recurrent/refractory solid tumors. Phase 2, utilizing Simon's optimal 2-stage design,&#xD;
      will be conducted to estimate the antitumor activity of lenvatinib in combination with&#xD;
      everolimus in pediatric participants with selected recurrent/refractory solid tumors&#xD;
      including Ewing sarcoma, rhabdomyosarcoma, and high grade glioma (HGG) using objective&#xD;
      response rate (ORR) at Week 16 as the outcome measure.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 16, 2017</start_date>
  <completion_date type="Actual">September 30, 2022</completion_date>
  <primary_completion_date type="Actual">September 30, 2022</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Phase 1: Maximum Tolerated Dose (MTD) of Lenvatinib in Combination With Everolimus</measure>
    <time_frame>Cycle 1 (Each cycle was of 28 days)</time_frame>
    <description>MTD was defined as the highest dose level at which no more than 1/6 participants experienced a dose limiting toxicity (DLTs), with the next higher dose having at least 0 of 3 or 1 of 6 participants experiencing DLTs. DLT was graded according to common terminology criteria for adverse events (CTCAE) version 4.03.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Phase 1: Recommended Phase 2 Dose (RP2D) of Lenvatinib in Combination With Everolimus</measure>
    <time_frame>Cycle 1 (Each cycle was of 28 days)</time_frame>
    <description>The RP2D of lenvatinib in combination with everolimus was determined by Dose Escalation Committee (DEC) based on safety (including DLTs), pharmacokinetic and clinical data. DLT was graded according to CTCAE v4.03.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Phase 1: Number of Participants With Any Treatment-emergent Adverse Event (TEAE)</measure>
    <time_frame>From date of first dose up to 28 days after the last dose of study treatment (Up to 17.5 months)</time_frame>
    <description>A TEAE was defined as an adverse event that emerged during treatment, having been absent at pretreatment or reemerged during treatment, having been present at pretreatment but stopped before treatment, or worsened in severity during treatment relative to the pretreatment state, when the adverse event is continuous. An adverse event was defined as any untoward medical occurrence in a participant administered an investigational product.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Phase 1: Number of Participants With Any Treatment-emergent Serious Adverse Event (TESAE)</measure>
    <time_frame>From date of first dose up to 28 days after the last dose of study treatment (Up to 17.5 months)</time_frame>
    <description>A TESAE was any untoward medical occurrence that at any dose: resulted in death; life threatening condition; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect or was medically important due to other reasons than the above mentioned criteria. An adverse event was defined as any untoward medical occurrence in a participant administered an investigational product.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Phase 2: Objective Response Rate (ORR) at Week 16</measure>
    <time_frame>Week 16</time_frame>
    <description>ORR at Week 16 was defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) at Week 16 based on investigator assessment according to response evaluation criteria in solid tumors (RECIST) version 1.1 for non-HGG cohorts and response assessment in neuro-oncology (RANO) for HGG cohort. CR was defined as disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis less than (&lt;) 10 millimeter (mm). PR was defined as at least a 30 percent (%) decrease in the sum of diameter (SOD) of target lesions, taking as reference the baseline sum diameters.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Phase 1: Objective Response Rate (ORR)</measure>
    <time_frame>From the date of the first dose of study drug to the date of first documentation of disease progression or death, whichever occurred first (up to 16.5 months)</time_frame>
    <description>ORR was defined as the percentage of participants with BOR of CR or PR based on investigator assessment according to RECIST version 1.1 for non-HGG cohorts and RANO for HGG cohort. CR was defined as disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis &lt;10 mm. PR was defined as at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2: Objective Response Rate (ORR)</measure>
    <time_frame>From the date of the first dose of study drug to the date of first documentation of disease progression or death, which ever occurred first (up to 6.5 months)</time_frame>
    <description>ORR was defined as the percentage of participants with BOR of CR or PR based on investigator assessment according to RECIST version 1.1 for non-HGG cohorts and RANO for HGG cohort. CR was defined as disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis &lt;10 mm. PR was defined as at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1: Disease Control Rate (DCR)</measure>
    <time_frame>From first dose of study drug until PD or death, whichever occurred first (up to 16.5 months)</time_frame>
    <description>DCR was defined as percentage of participants with a confirmed CR, PR, or stable disease (SD) (SD duration &gt;=7 weeks since the first dose of study treatment) divided by number of participants in analysis set. DCR was assessed by an investigator based on RECIST v1.1 for non-HGG participants or RANO for HGG participants. CR: disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis &lt;10 mm. PR: at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SOD. PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2: Disease Control Rate (DCR)</measure>
    <time_frame>From first dose of study drug until PD or death, whichever occurred first (up to 6.5 months)</time_frame>
    <description>DCR was defined as percentage of participants with confirmed CR, PR, or SD (SD duration greater than or equal to [&gt;=] 7 weeks since first dose of study treatment) divided by number of participants in analysis set. DCR was assessed by investigator based on RECIST v1.1 for non-HGG cohorts or RANO for HGG cohort. CR: disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis &lt;10 mm. PR: at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SOD. PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1: Clinical Benefit Rate (CBR)</measure>
    <time_frame>From first dose of study drug until PD or death, whichever occurred first (up to 16.5 months)</time_frame>
    <description>CBR was defined as percentage of participants who had BOR of CR, PR, or durable SD (SD duration &gt;=23 weeks since the first dose of study treatment) divided by number of participants in analysis set. CBR was assessed by an investigator based on RECIST v1.1 for non-HGG participants or RANO for HGG participants. CR: disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis &lt;10 mm. PR: at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SOD. PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2: Clinical Benefit Rate (CBR)</measure>
    <time_frame>From first dose of study drug until PD or death, whichever occurred first (up to 6.5 months)</time_frame>
    <description>CBR was defined as percentage of participants who had BOR of CR, PR, or durable SD (SD duration &gt;=23 weeks since the first dose of study treatment) divided by number of participants in analysis set. CBR was assessed by an investigator based on RECIST v1.1 for non-HGG cohorts or RANO for HGG cohort. CR: disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis &lt;10 mm. PR: at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SOD. PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1: Duration of Response (DOR)</measure>
    <time_frame>From date of the first observation of CR or PR until the date of first observation of progression or date of death (up to 16.5 months)</time_frame>
    <description>DOR was defined as the time (in months) from the date of first observation of confirmed response (PR or CR) to the date of the first observation of progression based on the investigator's assessment utilizing RECIST 1.1 for non-HGG cohorts and RANO for HGG cohorts, or date of death, whatever the cause. CR: disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis &lt;10 mm. PR: at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. PD was defined as at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2: Duration of Response (DOR)</measure>
    <time_frame>From date of the first observation of CR or PR until the date of first observation of progression or date of death (up to 6.5 months)</time_frame>
    <description>DOR was defined as the time (in months) from the date of first observation of confirmed response (PR or CR) to the date of the first observation of progression based on the investigator's assessment utilizing RECIST 1.1 for non-HGG cohorts and RANO for HGG cohort, or date of death, whatever the cause. CR: disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis &lt;10 mm. PR: at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. PD was defined as at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1: Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration of Lenvatinib (AUC[0-t Hours])</measure>
    <time_frame>Cycle 1 Days 1 and 15: 0-8 hours post-dose (Cycle length=28 days)</time_frame>
    <description>AUC0-t of lenvatinib was quantified using validated liquid chromatography tandem mass spectrometry (LC-MS/MS) methods.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1: Maximum Plasma Concentration of Lenvatinib (Cmax)</measure>
    <time_frame>Cycle 1 Days 1 and 15: 0-8 hours post-dose (Cycle length=28 days)</time_frame>
    <description>Cmax of lenvatinib was quantified using validated liquid LC-MS/MS methods.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1: Time to Reach Maximum Plasma Concentration (Cmax) of Lenvatinib (Tmax)</measure>
    <time_frame>Cycle 1 Days 1 and 15: 0-8 hours post-dose (Cycle length=28 days)</time_frame>
    <description>Tmax of lenvatinib was quantified using validated liquid LC-MS/MS methods.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1: Trough Concentrations (Ctrough) of Everolimus When Administered in Combination With Lenvatinib</measure>
    <time_frame>Cycle 1 Days 1, 2, 15 and 22: Pre-dose (Cycle length=28 days)</time_frame>
    <description>Trough concentrations of everolimus was quantified using validated liquid LC-MS/MS methods.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2: Number of Participants With Any Treatment-emergent Adverse Event (TEAE)</measure>
    <time_frame>From date of first dose up to 28 days after the last dose of study treatment (up to 7.5 months)</time_frame>
    <description>A TEAE was defined as an adverse event that emerged during treatment, having been absent at pretreatment or reemerged during treatment, having been present at pretreatment but stopped before treatment, or worsened in severity during treatment relative to the pretreatment state, when the adverse event is continuous. An adverse event was defined as any untoward medical occurrence in a participant administered an investigational product.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2: Number of Participants With Any Treatment-emergent Serious Adverse Event (TESAE)</measure>
    <time_frame>From date of first dose up to 28 days after the last dose of study treatment (up to 7.5 months)</time_frame>
    <description>A TESAE was any untoward medical occurrence that at any dose: resulted in death; life threatening condition; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect or was medically important due to other reasons than the above mentioned criteria. An adverse event was defined as any untoward medical occurrence in a participant administered an investigational product.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">64</enrollment>
  <condition>Recurrent and Refractory Solid Tumors</condition>
  <arm_group>
    <arm_group_label>Phase 1: Phase 1; Recurrent or refractory solid tumors</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>During Phase 1 (Treatment Phase: 1 cycle; 28 days of treatment), utilizing a rolling 6 design, participants with recurrent or refractory solid tumors will receive escalating doses of lenvatinib in combination with everolimus for determination of the maximum tolerated dose (MTD) and the recommended Phase 2 dose (RP2D). Participants who complete 1 cycle of treatment will transition to the Extension Phase, in which they will continue to receive the same study treatment in 28-day cycles.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Phase 2: Cohort 1, Ewing sarcoma</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>During Phase 2 (four 28-day cycles [up to 16 weeks of treatment]), utilizing Simon's optimal 2-stage design, participants with recurrent or refractory Ewing sarcoma (Cohort 1) will receive the RP2D of lenvatinib in combination with everolimus determined in Phase 1. Participants who discontinue study treatment before completing 4 cycles will transition to the Off-treatment Visit. Participants who complete 4 cycles will transition to the Extension Phase, in which they will continue to receive the same study treatment in 28-day cycles.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Phase 2: Cohort 2, Rhabdomyosarcoma</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>During Phase 2 (four 28-day cycles [up to 16 weeks of treatment]), utilizing Simon's optimal 2-stage design, participants with recurrent or refractory rhabdomyosarcoma (Cohort 2) will receive the RP2D of lenvatinib in combination with everolimus determined in Phase 1 (1 cycle; 4 weeks of treatment). Participants who discontinue study treatment before completing 4 cycles will transition to the Off-treatment Visit. Participants who complete 4 cycles will transition to the Extension Phase, in which they will continue to receive the same study treatment in 28-day cycles.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Phase 2: Cohort 3, High Grade Glioma (HGG)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>During Phase 2 (four 28-day cycles [up to 16 weeks of treatment]), utilizing Simon's optimal 2-stage design, participants with recurrent or refractory HGG (Cohort 3) will receive the RP2D of lenvatinib in combination with everolimus determined in Phase 1 (1 cycle; 4 weeks). Participants who discontinue study treatment before completing 4 cycles will transition to the Off-treatment Visit. Participants who complete 4 cycles will transition to the Extension Phase, in which they will continue to receive the same study treatment in 28-day cycles.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lenvatinib</intervention_name>
    <description>oral hard capsules containing 1 mg, 4 mg, or 10 mg lenvatinib, or an extemporaneous suspension</description>
    <arm_group_label>Phase 1: Phase 1; Recurrent or refractory solid tumors</arm_group_label>
    <arm_group_label>Phase 2: Cohort 1, Ewing sarcoma</arm_group_label>
    <arm_group_label>Phase 2: Cohort 2, Rhabdomyosarcoma</arm_group_label>
    <arm_group_label>Phase 2: Cohort 3, High Grade Glioma (HGG)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Everolimus</intervention_name>
    <description>2 mg, 3 mg, or 5 mg tablets for oral suspension</description>
    <arm_group_label>Phase 1: Phase 1; Recurrent or refractory solid tumors</arm_group_label>
    <arm_group_label>Phase 2: Cohort 1, Ewing sarcoma</arm_group_label>
    <arm_group_label>Phase 2: Cohort 2, Rhabdomyosarcoma</arm_group_label>
    <arm_group_label>Phase 2: Cohort 3, High Grade Glioma (HGG)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria&#xD;
&#xD;
          -  ≥2 years and &lt;18 years of age for enrolment in Phase 1 or ≥2 years and ≤21 years of&#xD;
             age for enrolment in Phase 2.&#xD;
&#xD;
          -  Recurrent or refractory solid tumors&#xD;
&#xD;
               -  Phase 1: All solid tumors (measurable or evaluable disease), including primary&#xD;
                  central nervous system (CNS) tumors; exclusion of hepatoblastoma and lymphomas.&#xD;
                  Participants with diffuse intrinsic pontine glioma, optic pathway glioma, or&#xD;
                  pineal tumors with elevated tumor markers (alpha-fetoprotein [AFP] and beta-human&#xD;
                  chorionic gonadotropin [ß-hCG][or human chorionic gonadotropin [hCG])do not&#xD;
                  require histological or cytological confirmation of diagnosis&#xD;
&#xD;
               -  Phase 2: Ewing sarcoma, Rhabdomyosarcoma, High Grade Glioma (HGG) (all must have&#xD;
                  measurable disease); exclusion of Diffuse Intrinsic Pontine Glioma&#xD;
&#xD;
          -  Histologically or cytologically confirmed diagnosis&#xD;
&#xD;
          -  Measurable disease that meets the following criteria (Phase 2):&#xD;
&#xD;
               1. RECIST 1.1 (for all tumor types except HGG): At least 1 lesion of ≥1.0 cm in the&#xD;
                  longest diameter for a non lymph node or ≥1.5 cm in the short-axis diameter for a&#xD;
                  lymph node which is serially measurable according to RECIST 1.1 using computed&#xD;
                  tomography /magnetic resonance imaging (CT/MRI)&#xD;
&#xD;
               2. Response Assessment in Neuro-Oncology (RANO) for high grade glioma (HGG): At&#xD;
                  least one lesion must be measurable as defined as a bi dimensionally contrast&#xD;
                  enhancing lesion with clearly defined margins by CT or MRI scan, with a minimal&#xD;
                  diameter of 1 cm, and visible on 2 axial slices which are preferably at most 5 mm&#xD;
                  apart with 0 mm skip&#xD;
&#xD;
        Lesions that have had external beam radiotherapy (EBRT) or locoregional therapies such as&#xD;
        radiofrequency (RF) ablation must show evidence of progressive disease based on RECIST 1.1&#xD;
        to be deemed a target lesion&#xD;
&#xD;
          -  Karnofsky performance score ≥50 for participants&gt;16 year of age and Lansky play score&#xD;
             ≥50 for participants ≤16 years of age. Neurologic deficits in participants with CNS&#xD;
             tumors must have been relatively stable for at least 7 days prior to study enrollment.&#xD;
             Participants who are unable to walk because of paralysis, but who are up in a&#xD;
             wheelchair, will be considered ambulatory for the purpose of assessing the performance&#xD;
             score&#xD;
&#xD;
          -  Prior Therapy&#xD;
&#xD;
               -  Participants must have fully recovered from the acute toxic effects of all prior&#xD;
                  anti-cancer therapy&#xD;
&#xD;
               -  Cytotoxic chemotherapy or other chemotherapy known to be myelosuppressive: ≥21&#xD;
                  days after the last dose of cytotoxic or myelosuppressive chemotherapy (42 days&#xD;
                  if prior nitrosourea)&#xD;
&#xD;
               -  Anti-cancer agents not known to be myelosuppressive (eg, not associated with&#xD;
                  reduced platelet or absolute neutrophil counts): ≥7 days after the last dose of&#xD;
                  agent&#xD;
&#xD;
               -  Monoclonal antibodies: ≥21 days or 3 half-lives (whichever is shorter) of the&#xD;
                  antibody must have elapsed after the last dose of a monoclonal antibody&#xD;
                  (including checkpoint inhibitors). Toxicity related to prior antibody therapy&#xD;
                  must be recovered to Grade ≤1&#xD;
&#xD;
               -  Corticosteroids: If used to modify immune adverse events related to prior&#xD;
                  therapy, ≥14 days must have elapsed since last dose of corticosteroid.&#xD;
                  Participants receiving corticosteroids, who have not been on a stable or&#xD;
                  decreasing dose of corticosteroid for at least 7 days prior to enrollment, are&#xD;
                  not eligible&#xD;
&#xD;
               -  Hematopoietic growth factors: ≥14 days after the last dose of a long-acting&#xD;
                  growth factor or 7 days for short-acting growth factor. For agents that have&#xD;
                  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&#xD;
&#xD;
               -  Interleukins, interferons, and cytokines (other than hematopoietic growth&#xD;
                  factors): ≥21 days after the completion of interleukins, interferons or cytokines&#xD;
                  (other than hematopoietic growth factors)&#xD;
&#xD;
               -  Stem cell infusions (with or without total body irradiation): Allogeneic&#xD;
                  (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion&#xD;
                  including donor leukocytes infusion or boost infusion: ≥84 days after infusion&#xD;
                  and no evidence of graft versus host disease; Autologous stem cell infusion&#xD;
                  including boost infusion: ≥42 days&#xD;
&#xD;
               -  Cellular Therapy: ≥42 days after the completion of any type of cellular therapy&#xD;
                  (eg, modified T cells, natural killer cells, dendritic cells, etc)&#xD;
&#xD;
               -  Radiotherapy (XRT)/External Beam Irradiation including Protons: ≥14 days after&#xD;
                  local XRT; ≥150 days after total body irradiation, craniospinal XRT or if&#xD;
                  radiation to ≥50% of the pelvis; ≥42 days if other substantial bone marrow&#xD;
                  radiation.&#xD;
&#xD;
               -  Radiopharmaceutical therapy: ≥42 days after systemically administered therapy.&#xD;
&#xD;
               -  Vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR)-targeted or&#xD;
                  mammalian target of rapamycin (mTOR)-targeted therapies: Must not have received&#xD;
                  prior exposure to lenvatinib; May have previously progressed on an mTOR&#xD;
                  inhibitor; No more than 2 prior VEGF/VEGFR-targeted therapies (For Phase 2 only);&#xD;
                  Must not have received prior VEGF/VEGFR-targeted therapy in combination with an&#xD;
                  mTOR inhibitor (For Phase 2 only)&#xD;
&#xD;
          -  Adequate bone marrow function for participants with solid tumors without known bone&#xD;
             marrow involvement&#xD;
&#xD;
          -  Adequate bone marrow function for participants with known bone marrow metastatic&#xD;
             disease&#xD;
&#xD;
          -  Adequate renal function&#xD;
&#xD;
          -  Adequate liver function&#xD;
&#xD;
          -  Adequate cardiac function&#xD;
&#xD;
          -  Adequate neurologic function&#xD;
&#xD;
          -  Adequate blood pressure (BP) control with or without antihypertensive medications&#xD;
&#xD;
          -  Adequate coagulation&#xD;
&#xD;
          -  Adequate pancreatic function&#xD;
&#xD;
          -  Adequate metabolic function&#xD;
&#xD;
          -  Adequate glycemic control&#xD;
&#xD;
          -  Participants must have a minimum body surface area (BSA) of 0.6 m^2 at study entry.&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
          -  Participants who have had or are planning to have the following invasive procedures&#xD;
&#xD;
               -  Major surgical procedure, laparoscopic procedure, open biopsy or significant&#xD;
                  traumatic injury within 28 days prior to enrolment&#xD;
&#xD;
               -  Central line placement or subcutaneous port 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;
               -  Fine needle aspirate within 7 days prior to enrolment&#xD;
&#xD;
               -  Surgical or other wounds must be adequately healed prior to enrolment&#xD;
&#xD;
               -  For purposes of this study, bone marrow aspirate and biopsy are not considered&#xD;
                  surgical procedures and therefore are permitted within 14 days prior to start of&#xD;
                  protocol therapy&#xD;
&#xD;
          -  Participants who have non-healing wound, unhealed or incompletely healed fracture, or&#xD;
             a compound (open) bone fracture at the time of enrolment&#xD;
&#xD;
          -  Participants having an active infection requiring systemic therapy.&#xD;
&#xD;
          -  Participants with a known history of active hepatitis B (defined as hepatitis B&#xD;
             surface antigen reactive or hepatitis B virus- deoxyribonucleic [DNA] detected) or&#xD;
             known active hepatitis C virus (HCV, defined as HCV- Ribonucleic acid [RNA] detected).&#xD;
             Note: No testing for hepatitis B and hepatitis C is required unless mandated by the&#xD;
             local health authority.&#xD;
&#xD;
          -  Known to be human immunodeficiency virus (HIV) positive. Note: HIV testing is required&#xD;
             at screening only when mandated by the local health authority&#xD;
&#xD;
          -  Clinical evidence of nephrotic syndrome prior to enrolment&#xD;
&#xD;
          -  Gastrointestinal bleeding or active hemoptysis (bright red blood of at least half&#xD;
             teaspoon) within 21 days prior to enrolment&#xD;
&#xD;
          -  Thrombotic/ thromboembolic event requiring systemic anticoagulation within 90 days&#xD;
             prior to enrollment&#xD;
&#xD;
          -  Evidence of new intracranial hemorrhage of more than punctate size on MRI assessment&#xD;
             obtained within 28 days prior to study enrollment for Participants with HGG&#xD;
&#xD;
          -  Diagnosis of lymphoma&#xD;
&#xD;
          -  Radiographic evidence of major blood vessel invasion/infiltration.&#xD;
&#xD;
          -  Evidence of untreated CNS metastases (exception: participants with primary CNS tumors&#xD;
             and leptomeningeal disease)&#xD;
&#xD;
          -  Participants who are currently receiving enzyme-inducing anticonvulsants&#xD;
&#xD;
          -  Participants chronically receiving strong cytochrome P450 3A4 (CYP3A4)/P-glycoprotein&#xD;
             (P-gp) inhibitors or inducers within 7 days prior to study enrollment&#xD;
&#xD;
          -  Females who are breastfeeding or pregnant. For females of childbearing potential, a&#xD;
             negative screening pregnancy test must be obtained within 72 hours before the first&#xD;
             dose of study drug&#xD;
&#xD;
          -  Males who have not had a successful vasectomy (confirmed azoospermia) or if they and&#xD;
             their female partners do not meet the criteria above (that is, not of childbearing&#xD;
             potential or practicing highly effective contraception throughout the study period and&#xD;
             for 7 days after lenvatinib discontinuation or 4 weeks after discontinuation of&#xD;
             everolimus). No sperm donation is allowed during the study period and for 7 days after&#xD;
             lenvatinib discontinuation or 4 weeks after discontinuation of everolimus.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>2 Years</minimum_age>
    <maximum_age>21 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <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>Phoenix Children's Hospital</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Loma Linda University Medical Center</name>
      <address>
        <city>Loma Linda</city>
        <state>California</state>
        <zip>92350</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Miller Children's and Women's Hospital</name>
      <address>
        <city>Long Beach</city>
        <state>California</state>
        <zip>90806</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital of Los Angeles</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90027</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Southern California Permanente Medical Group</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90027</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaiser Permenente</name>
      <address>
        <city>Oakland</city>
        <state>California</state>
        <zip>94611</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 at Mission Bay - Pediatric Oncology</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>Nemours/ Alfred I. duPont Hospital for Children</name>
      <address>
        <city>Wilmington</city>
        <state>Delaware</state>
        <zip>19803</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>Golisano Children's Hospital of Southwest Florida</name>
      <address>
        <city>Fort Myers</city>
        <state>Florida</state>
        <zip>33908</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Florida</name>
      <address>
        <city>Gainesville</city>
        <state>Florida</state>
        <zip>32610</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nicklaus Children's Hospital</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33155</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kapi'olani Medical Center</name>
      <address>
        <city>Honolulu</city>
        <state>Hawaii</state>
        <zip>96826</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St Jude Midwest Affiliate</name>
      <address>
        <city>Peoria</city>
        <state>Illinois</state>
        <zip>61637</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Riley Hospital for Children - Indiana University</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Louisville and Norton Children's Hospital</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Johns Hopkins</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21287</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>CS 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>University of Mississippi Medical Center</name>
      <address>
        <city>Jackson</city>
        <state>Mississippi</state>
        <zip>39216</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Mercy Hospital and Clinics</name>
      <address>
        <city>Kansas City</city>
        <state>Missouri</state>
        <zip>64108</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alliance for Childhood Diseases</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89135</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hackensack University Medical Center</name>
      <address>
        <city>Hackensack</city>
        <state>New Jersey</state>
        <zip>07601</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Morristown Medical Center</name>
      <address>
        <city>Morristown</city>
        <state>New Jersey</state>
        <zip>07960</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rutgers cancer Institute of NJ</name>
      <address>
        <city>New Brunswick</city>
        <state>New Jersey</state>
        <zip>08901</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cohen Children's Medical Center</name>
      <address>
        <city>New Hyde Park</city>
        <state>New York</state>
        <zip>11040</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Columbia University/Herbert Irving 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>Memorial Sloan Kettering Cancer Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>New York Medical College</name>
      <address>
        <city>Valhalla</city>
        <state>New York</state>
        <zip>10595</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>Nationwide Children's Hospital</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Oklahoma Health Sciences Center</name>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <zip>73104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oregon Health &amp; Science University</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239</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>Vanderbilt University Medical Center</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dell Children's Medical Center of Central Texas</name>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <zip>78723</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The University of Texas Southwestern Medical Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cook Children's Medical Center</name>
      <address>
        <city>Fort Worth</city>
        <state>Texas</state>
        <zip>76104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Children's Hospital</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Children's Hospital of San Antonio</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78207</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital of The King's Daughters</name>
      <address>
        <city>Norfolk</city>
        <state>Virginia</state>
        <zip>23507</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>
    <facility>
      <name>IWK Health Centre</name>
      <address>
        <city>Halifax</city>
        <state>Nova Scotia</state>
        <zip>B3K 6R8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital for Sick Children</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 1X8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Montreal Children's Hospital</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H4A3J1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Palau</country>
  </removed_countries>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>August 3, 2017</study_first_submitted>
  <study_first_submitted_qc>August 7, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 10, 2017</study_first_posted>
  <results_first_submitted>August 7, 2023</results_first_submitted>
  <results_first_submitted_qc>August 7, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">August 30, 2023</results_first_posted>
  <last_update_submitted>August 7, 2023</last_update_submitted>
  <last_update_submitted_qc>August 7, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 30, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>pediatrics</keyword>
  <keyword>central nervous system tumors</keyword>
  <keyword>lenvatinib</keyword>
  <keyword>E7080</keyword>
  <keyword>everolimus</keyword>
  <keyword>Ewing sarcoma/peripheral primitive neuroectodermal tumor</keyword>
  <keyword>rhabdomyosarcoma</keyword>
  <keyword>high grade glioma</keyword>
  <keyword>solid tumors</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <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>Everolimus</mesh_term>
    <mesh_term>Lenvatinib</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>August 16, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/51/NCT03245151/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>September 22, 2022</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/51/NCT03245151/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants took part in the study at 24 investigative sites in the United States and Canada from 16 November 2017 to 30 September 2022.</recruitment_details>
      <pre_assignment_details>A total of 86 participants were screened, out of which 64 were enrolled and 9 participants completed the study.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Phase 1: Lenvatinib 8 mg/m^2 + Everolimus 3 mg/m^2</title>
          <description>Participants with recurrent or refractory solid tumors received lenvatinib 8 milligram per square meter (mg/m^2), capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily in cycle 1 (each cycle was 28 days) until the occurrence of disease progression (PD), clinical benefit, development of unacceptable toxicity leading to withdrawal from the study, study discontinuation or for a maximum of 18 cycles (each cycle was 28 days) whichever occurred first.</description>
        </group>
        <group group_id="P2">
          <title>Phase 1: Lenvatinib 11 mg/m^2 + Everolimus 3 mg/m^2</title>
          <description>Participants with recurrent or refractory solid tumors received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily in cycle 1 (each cycle was 28 days) until the occurrence of PD, clinical benefit, development of unacceptable toxicity leading to withdrawal from the study, study discontinuation or for a maximum of 18 cycles (each cycle was 28 days) whichever occurred first.</description>
        </group>
        <group group_id="P3">
          <title>Phase 2: Cohort 1, Ewing Sarcoma</title>
          <description>Participants with recurrent or refractory ewing sarcoma received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily for up to 7 cycles (each cycle was 28 days) unless participant discontinued early from the study.</description>
        </group>
        <group group_id="P4">
          <title>Phase 2: Cohort 2, Rhabdomyosarcoma</title>
          <description>Participants with recurrent or refractory rhabdomyosarcoma received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily for up to 7 cycles (each cycle was 28 days) unless participant discontinued early from the study.</description>
        </group>
        <group group_id="P5">
          <title>Phase 2: Cohort 3, HGG</title>
          <description>Participants with recurrent or refractory high grade glioma (HGG) received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily for up to 7 cycles (each cycle was 28 days) unless participant discontinued early from the study.</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="18"/>
                <participants group_id="P3" count="10"/>
                <participants group_id="P4" count="20"/>
                <participants group_id="P5" count="11"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="2"/>
                <participants group_id="P5" count="3"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="15"/>
                <participants group_id="P3" count="9"/>
                <participants group_id="P4" count="18"/>
                <participants group_id="P5" count="8"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="2"/>
                <participants group_id="P5" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="14"/>
                <participants group_id="P3" count="9"/>
                <participants group_id="P4" count="16"/>
                <participants group_id="P5" count="7"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Sponsor's decision</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Safety Analysis Set (SAS) included all participants who received at least 1 dose of study drug (lenvatinib or everolimus).</population>
      <group_list>
        <group group_id="B1">
          <title>Phase 1: Lenvatinib 8 mg/m^2 + Everolimus 3 mg/m^2</title>
          <description>Participants with recurrent or refractory solid tumors received lenvatinib 8 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily in cycle 1 (each cycle was 28 days) until the occurrence of PD, clinical benefit, development of unacceptable toxicity leading to withdrawal from the study, study discontinuation or for a maximum of 18 cycles (each cycle was 28 days) whichever occurred first.</description>
        </group>
        <group group_id="B2">
          <title>Phase 1: Lenvatinib 11 mg/m^2 + Everolimus 3 mg/m^2</title>
          <description>Participants with recurrent or refractory solid tumors received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily in cycle 1 (each cycle was 28 days) until the occurrence of PD, clinical benefit, development of unacceptable toxicity leading to withdrawal from the study, study discontinuation or for a maximum of 18 cycles (each cycle was 28 days) whichever occurred first.</description>
        </group>
        <group group_id="B3">
          <title>Phase 2: Cohort 1, Ewing Sarcoma</title>
          <description>Participants with recurrent or refractory ewing sarcoma received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily for up to 7 cycles (each cycle was 28 days) unless participant discontinued early from the study.</description>
        </group>
        <group group_id="B4">
          <title>Phase 2: Cohort 2, Rhabdomyosarcoma</title>
          <description>Participants with recurrent or refractory rhabdomyosarcoma received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily for up to 7 cycles (each cycle was 28 days) unless participant discontinued early from the study.</description>
        </group>
        <group group_id="B5">
          <title>Phase 2: Cohort 3, HGG</title>
          <description>Participants with recurrent or refractory HGG received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily for up to 7 cycles (each cycle was 28 days) unless participant discontinued early from the study.</description>
        </group>
        <group group_id="B6">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="5"/>
            <count group_id="B2" value="18"/>
            <count group_id="B3" value="10"/>
            <count group_id="B4" value="20"/>
            <count group_id="B5" value="11"/>
            <count group_id="B6" value="64"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>2-11 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="9"/>
                    <measurement group_id="B5" value="3"/>
                    <measurement group_id="B6" value="31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>12-17 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="6"/>
                    <measurement group_id="B5" value="7"/>
                    <measurement group_id="B6" value="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>18-64 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="5"/>
                    <measurement group_id="B5" value="1"/>
                    <measurement group_id="B6" value="12"/>
                  </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="2"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="8"/>
                    <measurement group_id="B5" value="8"/>
                    <measurement group_id="B6" value="31"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="7"/>
                    <measurement group_id="B4" value="12"/>
                    <measurement group_id="B5" value="3"/>
                    <measurement group_id="B6" value="33"/>
                  </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="1"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="8"/>
                    <measurement group_id="B4" value="18"/>
                    <measurement group_id="B5" value="11"/>
                    <measurement group_id="B6" value="52"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <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="0"/>
                    <measurement group_id="B6" 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 group_id="B6" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="3"/>
                    <measurement group_id="B6" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="9"/>
                    <measurement group_id="B4" value="16"/>
                    <measurement group_id="B5" value="6"/>
                    <measurement group_id="B6" value="45"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="3"/>
                    <measurement group_id="B5" value="2"/>
                    <measurement group_id="B6" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Phase 1: Maximum Tolerated Dose (MTD) of Lenvatinib in Combination With Everolimus</title>
        <description>MTD was defined as the highest dose level at which no more than 1/6 participants experienced a dose limiting toxicity (DLTs), with the next higher dose having at least 0 of 3 or 1 of 6 participants experiencing DLTs. DLT was graded according to common terminology criteria for adverse events (CTCAE) version 4.03.</description>
        <time_frame>Cycle 1 (Each cycle was of 28 days)</time_frame>
        <population>SAS included all participants who received at least one dose of study drug (Lenvatinib or Everolimus).</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 1: Lenvatinib + Everolimus (All Participants)</title>
            <description>Participants with recurrent or refractory solid tumors received lenvatinib 8 or 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily in cycle 1 (each cycle was 28 days) until the occurrence of PD, clinical benefit, development of unacceptable toxicity leading to withdrawal from the study, study discontinuation or for a maximum of 18 cycles (each cycle was 28 days) whichever occurred first.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 1: Maximum Tolerated Dose (MTD) of Lenvatinib in Combination With Everolimus</title>
          <description>MTD was defined as the highest dose level at which no more than 1/6 participants experienced a dose limiting toxicity (DLTs), with the next higher dose having at least 0 of 3 or 1 of 6 participants experiencing DLTs. DLT was graded according to common terminology criteria for adverse events (CTCAE) version 4.03.</description>
          <population>SAS included all participants who received at least one dose of study drug (Lenvatinib or Everolimus).</population>
          <units>milligram per square meter (mg/m^2)</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Phase 1: Recommended Phase 2 Dose (RP2D) of Lenvatinib in Combination With Everolimus</title>
        <description>The RP2D of lenvatinib in combination with everolimus was determined by Dose Escalation Committee (DEC) based on safety (including DLTs), pharmacokinetic and clinical data. DLT was graded according to CTCAE v4.03.</description>
        <time_frame>Cycle 1 (Each cycle was of 28 days)</time_frame>
        <population>SAS included all participants who received at least one dose of study drug (Lenvatinib or Everolimus).</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 1: Lenvatinib + Everolimus (All Participants)</title>
            <description>Participants with recurrent or refractory solid tumors received lenvatinib 8 or 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily in cycle 1 (each cycle was 28 days) until the occurrence of PD, clinical benefit, development of unacceptable toxicity leading to withdrawal from the study, study discontinuation or for a maximum of 18 cycles (each cycle was 28 days) whichever occurred first.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 1: Recommended Phase 2 Dose (RP2D) of Lenvatinib in Combination With Everolimus</title>
          <description>The RP2D of lenvatinib in combination with everolimus was determined by Dose Escalation Committee (DEC) based on safety (including DLTs), pharmacokinetic and clinical data. DLT was graded according to CTCAE v4.03.</description>
          <population>SAS included all participants who received at least one dose of study drug (Lenvatinib or Everolimus).</population>
          <units>mg/m^2</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Phase 1: Number of Participants With Any Treatment-emergent Adverse Event (TEAE)</title>
        <description>A TEAE was defined as an adverse event that emerged during treatment, having been absent at pretreatment or reemerged during treatment, having been present at pretreatment but stopped before treatment, or worsened in severity during treatment relative to the pretreatment state, when the adverse event is continuous. An adverse event was defined as any untoward medical occurrence in a participant administered an investigational product.</description>
        <time_frame>From date of first dose up to 28 days after the last dose of study treatment (Up to 17.5 months)</time_frame>
        <population>SAS included all participants who received at least one dose of study drug (Lenvatinib or Everolimus).</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 1: Lenvatinib 8 mg/m^2 + Everolimus 3 mg/m^2</title>
            <description>Participants with recurrent or refractory solid tumors received lenvatinib 8 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily in cycle 1 (each cycle was 28 days) until the occurrence of PD, clinical benefit, development of unacceptable toxicity leading to withdrawal from the study, study discontinuation or for a maximum of 18 cycles (each cycle was 28 days) whichever occurred first.</description>
          </group>
          <group group_id="O2">
            <title>Phase 1: Lenvatinib 11 mg/m^2 + Everolimus 3 mg/m^2</title>
            <description>Participants with recurrent or refractory solid tumors received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily in cycle 1 (each cycle was 28 days) until the occurrence of PD, clinical benefit, development of unacceptable toxicity leading to withdrawal from the study, study discontinuation or for a maximum of 18 cycles (each cycle was 28 days) whichever occurred first.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 1: Number of Participants With Any Treatment-emergent Adverse Event (TEAE)</title>
          <description>A TEAE was defined as an adverse event that emerged during treatment, having been absent at pretreatment or reemerged during treatment, having been present at pretreatment but stopped before treatment, or worsened in severity during treatment relative to the pretreatment state, when the adverse event is continuous. An adverse event was defined as any untoward medical occurrence in a participant administered an investigational product.</description>
          <population>SAS included all participants who received at least one dose of study drug (Lenvatinib or Everolimus).</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="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Phase 1: Number of Participants With Any Treatment-emergent Serious Adverse Event (TESAE)</title>
        <description>A TESAE was any untoward medical occurrence that at any dose: resulted in death; life threatening condition; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect or was medically important due to other reasons than the above mentioned criteria. An adverse event was defined as any untoward medical occurrence in a participant administered an investigational product.</description>
        <time_frame>From date of first dose up to 28 days after the last dose of study treatment (Up to 17.5 months)</time_frame>
        <population>SAS included all participants who received at least one dose of study drug (Lenvatinib or Everolimus).</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 1: Lenvatinib 8 mg/m^2 + Everolimus 3 mg/m^2</title>
            <description>Participants with recurrent or refractory solid tumors received lenvatinib 8 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily in cycle 1 (each cycle was 28 days) until the occurrence of PD, clinical benefit, development of unacceptable toxicity leading to withdrawal from the study, study discontinuation or for a maximum of 18 cycles (each cycle was 28 days) whichever occurred first.</description>
          </group>
          <group group_id="O2">
            <title>Phase 1: Lenvatinib 11 mg/m^2 + Everolimus 3 mg/m^2</title>
            <description>Participants with recurrent or refractory solid tumors received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily in cycle 1 (each cycle was 28 days) until the occurrence of PD, clinical benefit, development of unacceptable toxicity leading to withdrawal from the study, study discontinuation or for a maximum of 18 cycles (each cycle was 28 days) whichever occurred first.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 1: Number of Participants With Any Treatment-emergent Serious Adverse Event (TESAE)</title>
          <description>A TESAE was any untoward medical occurrence that at any dose: resulted in death; life threatening condition; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect or was medically important due to other reasons than the above mentioned criteria. An adverse event was defined as any untoward medical occurrence in a participant administered an investigational product.</description>
          <population>SAS included all participants who received at least one dose of study drug (Lenvatinib or Everolimus).</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="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Phase 2: Objective Response Rate (ORR) at Week 16</title>
        <description>ORR at Week 16 was defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) at Week 16 based on investigator assessment according to response evaluation criteria in solid tumors (RECIST) version 1.1 for non-HGG cohorts and response assessment in neuro-oncology (RANO) for HGG cohort. CR was defined as disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis less than (&lt;) 10 millimeter (mm). PR was defined as at least a 30 percent (%) decrease in the sum of diameter (SOD) of target lesions, taking as reference the baseline sum diameters.</description>
        <time_frame>Week 16</time_frame>
        <population>Evaluable analysis set included all evaluable participants who have measurable disease present at baseline, and at least one postbaseline efficacy assessment, unless they have discontinued prior to the first efficacy assessment due to progressive disease.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 2: Cohort 1, Ewing Sarcoma</title>
            <description>Participants with recurrent or refractory ewing sarcoma received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily for up to 7 cycles (each cycle was 28 days) unless participant discontinued early from the study.</description>
          </group>
          <group group_id="O2">
            <title>Phase 2: Cohort 2, Rhabdomyosarcoma</title>
            <description>Participants with recurrent or refractory rhabdomyosarcoma received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily for up to 7 cycles (each cycle was 28 days) unless participant discontinued early from the study.</description>
          </group>
          <group group_id="O3">
            <title>Phase 2: Cohort 3, HGG</title>
            <description>Participants with recurrent or refractory HGG received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily for up to 7 cycles (each cycle was 28 days) unless participant discontinued early from the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 2: Objective Response Rate (ORR) at Week 16</title>
          <description>ORR at Week 16 was defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) at Week 16 based on investigator assessment according to response evaluation criteria in solid tumors (RECIST) version 1.1 for non-HGG cohorts and response assessment in neuro-oncology (RANO) for HGG cohort. CR was defined as disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis less than (&lt;) 10 millimeter (mm). PR was defined as at least a 30 percent (%) decrease in the sum of diameter (SOD) of target lesions, taking as reference the baseline sum diameters.</description>
          <population>Evaluable analysis set included all evaluable participants who have measurable disease present at baseline, and at least one postbaseline efficacy assessment, unless they have discontinued prior to the first efficacy assessment due to progressive disease.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="20"/>
                <count group_id="O3" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" spread="0.0" lower_limit="0.0" upper_limit="30.8"/>
                    <measurement group_id="O2" value="10.0" spread="1.2" lower_limit="1.2" upper_limit="31.7"/>
                    <measurement group_id="O3" value="0" spread="0.0" lower_limit="0.0" upper_limit="30.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase 1: Objective Response Rate (ORR)</title>
        <description>ORR was defined as the percentage of participants with BOR of CR or PR based on investigator assessment according to RECIST version 1.1 for non-HGG cohorts and RANO for HGG cohort. CR was defined as disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis &lt;10 mm. PR was defined as at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters.</description>
        <time_frame>From the date of the first dose of study drug to the date of first documentation of disease progression or death, whichever occurred first (up to 16.5 months)</time_frame>
        <population>SAS included all participants who received at least 1 dose of study drug (lenvatinib or everolimus). Here, 'overall number of participants analyzed' signifies participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 1: Lenvatinib 8 mg/m^2 + Everolimus 3 mg/m^2</title>
            <description>Participants with recurrent or refractory solid tumors received lenvatinib 8 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily in cycle 1 (each cycle was 28 days) until the occurrence of PD, clinical benefit, development of unacceptable toxicity leading to withdrawal from the study, study discontinuation or for a maximum of 18 cycles (each cycle was 28 days) whichever occurred first.</description>
          </group>
          <group group_id="O2">
            <title>Phase 1: Lenvatinib 11 mg/m^2 + Everolimus 3 mg/m^2</title>
            <description>Participants with recurrent or refractory solid tumors received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily in cycle 1 (each cycle was 28 days) until the occurrence of PD, clinical benefit, development of unacceptable toxicity leading to withdrawal from the study, study discontinuation or for a maximum of 18 cycles (each cycle was 28 days) whichever occurred first.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 1: Objective Response Rate (ORR)</title>
          <description>ORR was defined as the percentage of participants with BOR of CR or PR based on investigator assessment according to RECIST version 1.1 for non-HGG cohorts and RANO for HGG cohort. CR was defined as disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis &lt;10 mm. PR was defined as at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters.</description>
          <population>SAS included all participants who received at least 1 dose of study drug (lenvatinib or everolimus). Here, 'overall number of participants analyzed' signifies participants who were evaluable for this outcome measure.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" spread="0.0" lower_limit="0.0" upper_limit="70.8"/>
                    <measurement group_id="O2" value="0.0" spread="0.0" lower_limit="0.0" upper_limit="21.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase 2: Objective Response Rate (ORR)</title>
        <description>ORR was defined as the percentage of participants with BOR of CR or PR based on investigator assessment according to RECIST version 1.1 for non-HGG cohorts and RANO for HGG cohort. CR was defined as disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis &lt;10 mm. PR was defined as at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters.</description>
        <time_frame>From the date of the first dose of study drug to the date of first documentation of disease progression or death, which ever occurred first (up to 6.5 months)</time_frame>
        <population>Evaluable analysis set included all evaluable participants who have measurable disease present at baseline, and at least one postbaseline efficacy assessment, unless they have discontinued prior to the first efficacy assessment due to progressive disease.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 2: Cohort 1, Ewing Sarcoma</title>
            <description>Participants with recurrent or refractory ewing sarcoma received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily for up to 7 cycles (each cycle was 28 days) unless participant discontinued early from the study.</description>
          </group>
          <group group_id="O2">
            <title>Phase 2: Cohort 2, Rhabdomyosarcoma</title>
            <description>Participants with recurrent or refractory rhabdomyosarcoma received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily for up to 7 cycles (each cycle was 28 days) unless participant discontinued early from the study.</description>
          </group>
          <group group_id="O3">
            <title>Phase 2: Cohort 3, HGG</title>
            <description>Participants with recurrent or refractory HGG received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily for up to 7 cycles (each cycle was 28 days) unless participant discontinued early from the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 2: Objective Response Rate (ORR)</title>
          <description>ORR was defined as the percentage of participants with BOR of CR or PR based on investigator assessment according to RECIST version 1.1 for non-HGG cohorts and RANO for HGG cohort. CR was defined as disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis &lt;10 mm. PR was defined as at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters.</description>
          <population>Evaluable analysis set included all evaluable participants who have measurable disease present at baseline, and at least one postbaseline efficacy assessment, unless they have discontinued prior to the first efficacy assessment due to progressive disease.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="20"/>
                <count group_id="O3" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" spread="0.0" lower_limit="0.0" upper_limit="30.8"/>
                    <measurement group_id="O2" value="10.0" spread="1.2" lower_limit="1.2" upper_limit="31.7"/>
                    <measurement group_id="O3" value="0.0" spread="0.0" lower_limit="0.0" upper_limit="30.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase 1: Disease Control Rate (DCR)</title>
        <description>DCR was defined as percentage of participants with a confirmed CR, PR, or stable disease (SD) (SD duration &gt;=7 weeks since the first dose of study treatment) divided by number of participants in analysis set. DCR was assessed by an investigator based on RECIST v1.1 for non-HGG participants or RANO for HGG participants. CR: disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis &lt;10 mm. PR: at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SOD. PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.</description>
        <time_frame>From first dose of study drug until PD or death, whichever occurred first (up to 16.5 months)</time_frame>
        <population>SAS included all participants who received at least 1 dose of study drug (lenvatinib or everolimus).</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 1: Lenvatinib 8 mg/m^2 + Everolimus 3 mg/m^2</title>
            <description>Participants with recurrent or refractory solid tumors received lenvatinib 8 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily in cycle 1 (each cycle was 28 days) until the occurrence of PD, clinical benefit, development of unacceptable toxicity leading to withdrawal from the study, study discontinuation or for a maximum of 18 cycles (each cycle was 28 days) whichever occurred first.</description>
          </group>
          <group group_id="O2">
            <title>Phase 1: Lenvatinib 11 mg/m^2 + Everolimus 3 mg/m^2</title>
            <description>Participants with recurrent or refractory solid tumors received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily in cycle 1 (each cycle was 28 days) until the occurrence of PD, clinical benefit, development of unacceptable toxicity leading to withdrawal from the study, study discontinuation or for a maximum of 18 cycles (each cycle was 28 days) whichever occurred first.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 1: Disease Control Rate (DCR)</title>
          <description>DCR was defined as percentage of participants with a confirmed CR, PR, or stable disease (SD) (SD duration &gt;=7 weeks since the first dose of study treatment) divided by number of participants in analysis set. DCR was assessed by an investigator based on RECIST v1.1 for non-HGG participants or RANO for HGG participants. CR: disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis &lt;10 mm. PR: at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SOD. PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.</description>
          <population>SAS included all participants who received at least 1 dose of study drug (lenvatinib or everolimus).</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20.0" spread="0.5" lower_limit="0.5" upper_limit="71.6"/>
                    <measurement group_id="O2" value="50.0" spread="26.0" lower_limit="26.0" upper_limit="74.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase 2: Disease Control Rate (DCR)</title>
        <description>DCR was defined as percentage of participants with confirmed CR, PR, or SD (SD duration greater than or equal to [&gt;=] 7 weeks since first dose of study treatment) divided by number of participants in analysis set. DCR was assessed by investigator based on RECIST v1.1 for non-HGG cohorts or RANO for HGG cohort. CR: disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis &lt;10 mm. PR: at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SOD. PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.</description>
        <time_frame>From first dose of study drug until PD or death, whichever occurred first (up to 6.5 months)</time_frame>
        <population>Evaluable analysis set included all evaluable participants who have measurable disease present at baseline, and at least one postbaseline efficacy assessment, unless they have discontinued prior to the first efficacy assessment due to progressive disease.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 2: Cohort 1, Ewing Sarcoma</title>
            <description>Participants with recurrent or refractory ewing sarcoma received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily for up to 7 cycles (each cycle was 28 days) unless participant discontinued early from the study.</description>
          </group>
          <group group_id="O2">
            <title>Phase 2: Cohort 2, Rhabdomyosarcoma</title>
            <description>Participants with recurrent or refractory rhabdomyosarcoma received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily for up to 7 cycles (each cycle was 28 days) unless participant discontinued early from the study.</description>
          </group>
          <group group_id="O3">
            <title>Phase 2: Cohort 3, HGG</title>
            <description>Participants with recurrent or refractory HGG received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily for up to 7 cycles (each cycle was 28 days) unless participant discontinued early from the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 2: Disease Control Rate (DCR)</title>
          <description>DCR was defined as percentage of participants with confirmed CR, PR, or SD (SD duration greater than or equal to [&gt;=] 7 weeks since first dose of study treatment) divided by number of participants in analysis set. DCR was assessed by investigator based on RECIST v1.1 for non-HGG cohorts or RANO for HGG cohort. CR: disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis &lt;10 mm. PR: at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SOD. PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.</description>
          <population>Evaluable analysis set included all evaluable participants who have measurable disease present at baseline, and at least one postbaseline efficacy assessment, unless they have discontinued prior to the first efficacy assessment due to progressive disease.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="20"/>
                <count group_id="O3" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="40.0" spread="12.2" lower_limit="12.2" upper_limit="73.8"/>
                    <measurement group_id="O2" value="40.0" spread="19.1" lower_limit="19.1" upper_limit="63.9"/>
                    <measurement group_id="O3" value="30.0" spread="6.7" lower_limit="6.7" upper_limit="65.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase 1: Clinical Benefit Rate (CBR)</title>
        <description>CBR was defined as percentage of participants who had BOR of CR, PR, or durable SD (SD duration &gt;=23 weeks since the first dose of study treatment) divided by number of participants in analysis set. CBR was assessed by an investigator based on RECIST v1.1 for non-HGG participants or RANO for HGG participants. CR: disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis &lt;10 mm. PR: at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SOD. PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.</description>
        <time_frame>From first dose of study drug until PD or death, whichever occurred first (up to 16.5 months)</time_frame>
        <population>SAS included all participants who received at least 1 dose of study drug (lenvatinib or everolimus).</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 1: Lenvatinib 8 mg/m^2 + Everolimus 3 mg/m^2</title>
            <description>Participants with recurrent or refractory solid tumors received lenvatinib 8 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily in cycle 1 (each cycle was 28 days) until the occurrence of PD, clinical benefit, development of unacceptable toxicity leading to withdrawal from the study, study discontinuation or for a maximum of 18 cycles (each cycle was 28 days) whichever occurred first.</description>
          </group>
          <group group_id="O2">
            <title>Phase 1: Lenvatinib 11 mg/m^2 + Everolimus 3 mg/m^2</title>
            <description>Participants with recurrent or refractory solid tumors received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily in cycle 1 (each cycle was 28 days) until the occurrence of PD, clinical benefit, development of unacceptable toxicity leading to withdrawal from the study, study discontinuation or for a maximum of 18 cycles (each cycle was 28 days) whichever occurred first.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 1: Clinical Benefit Rate (CBR)</title>
          <description>CBR was defined as percentage of participants who had BOR of CR, PR, or durable SD (SD duration &gt;=23 weeks since the first dose of study treatment) divided by number of participants in analysis set. CBR was assessed by an investigator based on RECIST v1.1 for non-HGG participants or RANO for HGG participants. CR: disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis &lt;10 mm. PR: at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SOD. PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.</description>
          <population>SAS included all participants who received at least 1 dose of study drug (lenvatinib or everolimus).</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20.0" spread="0.5" lower_limit="0.5" upper_limit="71.6"/>
                    <measurement group_id="O2" value="22.2" spread="6.4" lower_limit="6.4" upper_limit="47.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase 2: Clinical Benefit Rate (CBR)</title>
        <description>CBR was defined as percentage of participants who had BOR of CR, PR, or durable SD (SD duration &gt;=23 weeks since the first dose of study treatment) divided by number of participants in analysis set. CBR was assessed by an investigator based on RECIST v1.1 for non-HGG cohorts or RANO for HGG cohort. CR: disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis &lt;10 mm. PR: at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SOD. PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.</description>
        <time_frame>From first dose of study drug until PD or death, whichever occurred first (up to 6.5 months)</time_frame>
        <population>Evaluable analysis set included all evaluable participants who have measurable disease present at baseline, and at least one postbaseline efficacy assessment, unless they have discontinued prior to the first efficacy assessment due to PD.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 2: Cohort 1, Ewing Sarcoma</title>
            <description>Participants with recurrent or refractory ewing sarcoma received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily for up to 7 cycles (each cycle was 28 days) unless participant discontinued early from the study.</description>
          </group>
          <group group_id="O2">
            <title>Phase 2: Cohort 2, Rhabdomyosarcoma</title>
            <description>Participants with recurrent or refractory rhabdomyosarcoma received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily for up to 7 cycles (each cycle was 28 days) unless participant discontinued early from the study.</description>
          </group>
          <group group_id="O3">
            <title>Phase 2: Cohort 3, HGG</title>
            <description>Participants with recurrent or refractory HGG received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily for up to 7 cycles (each cycle was 28 days) unless participant discontinued early from the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 2: Clinical Benefit Rate (CBR)</title>
          <description>CBR was defined as percentage of participants who had BOR of CR, PR, or durable SD (SD duration &gt;=23 weeks since the first dose of study treatment) divided by number of participants in analysis set. CBR was assessed by an investigator based on RECIST v1.1 for non-HGG cohorts or RANO for HGG cohort. CR: disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis &lt;10 mm. PR: at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SOD. PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.</description>
          <population>Evaluable analysis set included all evaluable participants who have measurable disease present at baseline, and at least one postbaseline efficacy assessment, unless they have discontinued prior to the first efficacy assessment due to PD.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="20"/>
                <count group_id="O3" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20.0" spread="2.5" lower_limit="2.5" upper_limit="55.6"/>
                    <measurement group_id="O2" value="10.0" spread="1.2" lower_limit="1.2" upper_limit="31.7"/>
                    <measurement group_id="O3" value="0.0" spread="0.0" lower_limit="0.0" upper_limit="30.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase 1: Duration of Response (DOR)</title>
        <description>DOR was defined as the time (in months) from the date of first observation of confirmed response (PR or CR) to the date of the first observation of progression based on the investigator's assessment utilizing RECIST 1.1 for non-HGG cohorts and RANO for HGG cohorts, or date of death, whatever the cause. CR: disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis &lt;10 mm. PR: at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. PD was defined as at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.</description>
        <time_frame>From date of the first observation of CR or PR until the date of first observation of progression or date of death (up to 16.5 months)</time_frame>
        <population>SAS included all participants who received at least 1 dose of study drug (lenvatinib or everolimus). Here, 'overall number of participants analyzed' signifies participants who had CR or PR (0 participants hence, none were analyzed for this outcome measure).</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 1: Lenvatinib 8 mg/m^2 + Everolimus 3 mg/m^2</title>
            <description>Participants with recurrent or refractory solid tumors received lenvatinib 8 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily in cycle 1 (each cycle was 28 days) until the occurrence of PD, clinical benefit, development of unacceptable toxicity leading to withdrawal from the study, study discontinuation or for a maximum of 18 cycles (each cycle was 28 days) whichever occurred first.</description>
          </group>
          <group group_id="O2">
            <title>Phase 1: Lenvatinib 11 mg/m^2 + Everolimus 3 mg/m^2</title>
            <description>Participants with recurrent or refractory solid tumors received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily in cycle 1 (each cycle was 28 days) until the occurrence of PD, clinical benefit, development of unacceptable toxicity leading to withdrawal from the study, study discontinuation or for a maximum of 18 cycles (each cycle was 28 days) whichever occurred first.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 1: Duration of Response (DOR)</title>
          <description>DOR was defined as the time (in months) from the date of first observation of confirmed response (PR or CR) to the date of the first observation of progression based on the investigator's assessment utilizing RECIST 1.1 for non-HGG cohorts and RANO for HGG cohorts, or date of death, whatever the cause. CR: disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis &lt;10 mm. PR: at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. PD was defined as at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.</description>
          <population>SAS included all participants who received at least 1 dose of study drug (lenvatinib or everolimus). Here, 'overall number of participants analyzed' signifies participants who had CR or PR (0 participants hence, none were analyzed for this outcome measure).</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase 2: Duration of Response (DOR)</title>
        <description>DOR was defined as the time (in months) from the date of first observation of confirmed response (PR or CR) to the date of the first observation of progression based on the investigator's assessment utilizing RECIST 1.1 for non-HGG cohorts and RANO for HGG cohort, or date of death, whatever the cause. CR: disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis &lt;10 mm. PR: at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. PD was defined as at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.</description>
        <time_frame>From date of the first observation of CR or PR until the date of first observation of progression or date of death (up to 6.5 months)</time_frame>
        <population>Evaluable analysis set included all evaluable participants who have measurable disease present at baseline, and at least one postbaseline efficacy assessment, unless they have discontinued prior to first efficacy assessment due to progressive disease. Here, 'overall number of participants analyzed' signifies participants who had CR or PR.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 2: Cohort 1, Ewing Sarcoma</title>
            <description>Participants with recurrent or refractory ewing sarcoma received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily for up to 7 cycles (each cycle was 28 days) unless participant discontinued early from the study.</description>
          </group>
          <group group_id="O2">
            <title>Phase 2: Cohort 2, Rhabdomyosarcoma</title>
            <description>Participants with recurrent or refractory rhabdomyosarcoma received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily for up to 7 cycles (each cycle was 28 days) unless participant discontinued early from the study.</description>
          </group>
          <group group_id="O3">
            <title>Phase 2: Cohort 3, HGG</title>
            <description>Participants with recurrent or refractory HGG received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily for up to 7 cycles (each cycle was 28 days) unless participant discontinued early from the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 2: Duration of Response (DOR)</title>
          <description>DOR was defined as the time (in months) from the date of first observation of confirmed response (PR or CR) to the date of the first observation of progression based on the investigator's assessment utilizing RECIST 1.1 for non-HGG cohorts and RANO for HGG cohort, or date of death, whatever the cause. CR: disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis &lt;10 mm. PR: at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. PD was defined as at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.</description>
          <population>Evaluable analysis set included all evaluable participants who have measurable disease present at baseline, and at least one postbaseline efficacy assessment, unless they have discontinued prior to first efficacy assessment due to progressive disease. Here, 'overall number of participants analyzed' signifies participants who had CR or PR.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="2"/>
                <count group_id="O3" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="2.4" lower_limit="2.1" upper_limit="NA">Upper limit of 95% Confidence Interval could not be estimated as insufficient number of participants were available for analysis.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase 1: Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration of Lenvatinib (AUC[0-t Hours])</title>
        <description>AUC0-t of lenvatinib was quantified using validated liquid chromatography tandem mass spectrometry (LC-MS/MS) methods.</description>
        <time_frame>Cycle 1 Days 1 and 15: 0-8 hours post-dose (Cycle length=28 days)</time_frame>
        <population>Pharmacokinetic analysis set included participants who had at least one measurable postdose plasma concentration with an adequately documented drug administration history. Here, 'number analyzed' signifies participants who were evaluable for given timepoints of this outcome measure. Pharmacokinetic data was planned to be analyzed for Phase 1 only.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 1: Lenvatinib 8 mg/m^2 + Everolimus 3 mg/m^2</title>
            <description>Participants with recurrent or refractory solid tumors received lenvatinib 8 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily in cycle 1 (each cycle was 28 days) until the occurrence of PD, clinical benefit, development of unacceptable toxicity leading to withdrawal from the study, study discontinuation or for a maximum of 18 cycles (each cycle was 28 days) whichever occurred first.</description>
          </group>
          <group group_id="O2">
            <title>Phase 1: Lenvatinib 11 mg/m^2 + Everolimus 3 mg/m^2</title>
            <description>Participants with recurrent or refractory solid tumors received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily in cycle 1 (each cycle was 28 days) until the occurrence of PD, clinical benefit, development of unacceptable toxicity leading to withdrawal from the study, study discontinuation or for a maximum of 18 cycles (each cycle was 28 days) whichever occurred first.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 1: Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration of Lenvatinib (AUC[0-t Hours])</title>
          <description>AUC0-t of lenvatinib was quantified using validated liquid chromatography tandem mass spectrometry (LC-MS/MS) methods.</description>
          <population>Pharmacokinetic analysis set included participants who had at least one measurable postdose plasma concentration with an adequately documented drug administration history. Here, 'number analyzed' signifies participants who were evaluable for given timepoints of this outcome measure. Pharmacokinetic data was planned to be analyzed for Phase 1 only.</population>
          <units>nanogram*hour per milliliter (ng*hr/mL)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle 1 Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                    <count group_id="O2" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2338.0" spread="1633.41"/>
                    <measurement group_id="O2" value="3281.1" spread="1064.72"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 1 Day 15</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                    <count group_id="O2" value="17"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1328.0" spread="520.69"/>
                    <measurement group_id="O2" value="2139.8" spread="1156.48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase 1: Maximum Plasma Concentration of Lenvatinib (Cmax)</title>
        <description>Cmax of lenvatinib was quantified using validated liquid LC-MS/MS methods.</description>
        <time_frame>Cycle 1 Days 1 and 15: 0-8 hours post-dose (Cycle length=28 days)</time_frame>
        <population>Pharmacokinetic analysis set included participants who had at least one measurable postdose plasma concentration with an adequately documented drug administration history. Here, 'number analyzed' signifies participants who were evaluable for given timepoints of this outcome measure. Pharmacokinetic data was planned to be analyzed for Phase 1 only.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 1: Lenvatinib 8 mg/m^2 + Everolimus 3 mg/m^2</title>
            <description>Participants with recurrent or refractory solid tumors received lenvatinib 8 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily in cycle 1 (each cycle was 28 days) until the occurrence of PD, clinical benefit, development of unacceptable toxicity leading to withdrawal from the study, study discontinuation or for a maximum of 18 cycles (each cycle was 28 days) whichever occurred first.</description>
          </group>
          <group group_id="O2">
            <title>Phase 1: Lenvatinib 11 mg/m^2 + Everolimus 3 mg/m^2</title>
            <description>Participants with recurrent or refractory solid tumors received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily in cycle 1 (each cycle was 28 days) until the occurrence of PD, clinical benefit, development of unacceptable toxicity leading to withdrawal from the study, study discontinuation or for a maximum of 18 cycles (each cycle was 28 days) whichever occurred first.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 1: Maximum Plasma Concentration of Lenvatinib (Cmax)</title>
          <description>Cmax of lenvatinib was quantified using validated liquid LC-MS/MS methods.</description>
          <population>Pharmacokinetic analysis set included participants who had at least one measurable postdose plasma concentration with an adequately documented drug administration history. Here, 'number analyzed' signifies participants who were evaluable for given timepoints of this outcome measure. Pharmacokinetic data was planned to be analyzed for Phase 1 only.</population>
          <units>nanogram per milliliter (ng/mL)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle 1 Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                    <count group_id="O2" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="240.20" spread="130.892"/>
                    <measurement group_id="O2" value="404.13" spread="121.473"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 1 Day 15</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                    <count group_id="O2" value="17"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="314.20" spread="149.527"/>
                    <measurement group_id="O2" value="447.62" spread="272.790"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase 1: Time to Reach Maximum Plasma Concentration (Cmax) of Lenvatinib (Tmax)</title>
        <description>Tmax of lenvatinib was quantified using validated liquid LC-MS/MS methods.</description>
        <time_frame>Cycle 1 Days 1 and 15: 0-8 hours post-dose (Cycle length=28 days)</time_frame>
        <population>Pharmacokinetic analysis set included participants who had at least one measurable postdose plasma concentration with an adequately documented drug administration history. Here, 'number analyzed' signifies participants who were evaluable for given timepoints of this outcome measure. Pharmacokinetic data was planned to be analyzed for Phase 1 only.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 1: Lenvatinib 8 mg/m^2 + Everolimus 3 mg/m^2</title>
            <description>Participants with recurrent or refractory solid tumors received lenvatinib 8 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily in cycle 1 (each cycle was 28 days) until the occurrence of PD, clinical benefit, development of unacceptable toxicity leading to withdrawal from the study, study discontinuation or for a maximum of 18 cycles (each cycle was 28 days) whichever occurred first.</description>
          </group>
          <group group_id="O2">
            <title>Phase 1: Lenvatinib 11 mg/m^2 + Everolimus 3 mg/m^2</title>
            <description>Participants with recurrent or refractory solid tumors received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily in cycle 1 (each cycle was 28 days) until the occurrence of PD, clinical benefit, development of unacceptable toxicity leading to withdrawal from the study, study discontinuation or for a maximum of 18 cycles (each cycle was 28 days) whichever occurred first.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 1: Time to Reach Maximum Plasma Concentration (Cmax) of Lenvatinib (Tmax)</title>
          <description>Tmax of lenvatinib was quantified using validated liquid LC-MS/MS methods.</description>
          <population>Pharmacokinetic analysis set included participants who had at least one measurable postdose plasma concentration with an adequately documented drug administration history. Here, 'number analyzed' signifies participants who were evaluable for given timepoints of this outcome measure. Pharmacokinetic data was planned to be analyzed for Phase 1 only.</population>
          <units>hours</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle 1 Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                    <count group_id="O2" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.000" lower_limit="2.000" upper_limit="4.000"/>
                    <measurement group_id="O2" value="2.890" lower_limit="1.000" upper_limit="7.78"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 1 Day 15</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                    <count group_id="O2" value="17"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.950" lower_limit="2.000" upper_limit="8.05"/>
                    <measurement group_id="O2" value="2.950" lower_limit="0" upper_limit="8.02"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase 1: Trough Concentrations (Ctrough) of Everolimus When Administered in Combination With Lenvatinib</title>
        <description>Trough concentrations of everolimus was quantified using validated liquid LC-MS/MS methods.</description>
        <time_frame>Cycle 1 Days 1, 2, 15 and 22: Pre-dose (Cycle length=28 days)</time_frame>
        <population>Pharmacokinetic analysis set included participants who had at least one measurable postdose plasma concentration with an adequately documented drug administration history. Here, 'overall number of participants analyzed' signifies participants who were evaluable for this outcome measure and 'number analyzed' signifies participants who were evaluable for given timepoints of this outcome measure. Pharmacokinetic data was planned to be analyzed for Phase 1 only.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 1: Lenvatinib 8 mg/m^2 + Everolimus 3 mg/m^2</title>
            <description>Participants with recurrent or refractory solid tumors received lenvatinib 8 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily in cycle 1 (each cycle was 28 days) until the occurrence of PD, clinical benefit, development of unacceptable toxicity leading to withdrawal from the study, study discontinuation or for a maximum of 18 cycles (each cycle was 28 days) whichever occurred first.</description>
          </group>
          <group group_id="O2">
            <title>Phase 1: Lenvatinib 11 mg/m^2 + Everolimus 3 mg/m^2</title>
            <description>Participants with recurrent or refractory solid tumors received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily in cycle 1 (each cycle was 28 days) until the occurrence of PD, clinical benefit, development of unacceptable toxicity leading to withdrawal from the study, study discontinuation or for a maximum of 18 cycles (each cycle was 28 days) whichever occurred first.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 1: Trough Concentrations (Ctrough) of Everolimus When Administered in Combination With Lenvatinib</title>
          <description>Trough concentrations of everolimus was quantified using validated liquid LC-MS/MS methods.</description>
          <population>Pharmacokinetic analysis set included participants who had at least one measurable postdose plasma concentration with an adequately documented drug administration history. Here, 'overall number of participants analyzed' signifies participants who were evaluable for this outcome measure and 'number analyzed' signifies participants who were evaluable for given timepoints of this outcome measure. Pharmacokinetic data was planned to be analyzed for Phase 1 only.</population>
          <units>ng/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle 1 Day 1: Pre-dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                    <count group_id="O2" value="17"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" spread="0.0"/>
                    <measurement group_id="O2" value="0.0" spread="0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 1 Day 2: Pre-dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                    <count group_id="O2" value="17"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.1" spread="1.34"/>
                    <measurement group_id="O2" value="2.2" spread="1.13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 1 Day 15: Pre-dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                    <count group_id="O2" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.2" spread="2.42"/>
                    <measurement group_id="O2" value="5.1" spread="2.98"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 1 Day 22: Pre-dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                    <count group_id="O2" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.8" spread="1.96"/>
                    <measurement group_id="O2" value="4.2" spread="2.73"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase 2: Number of Participants With Any Treatment-emergent Adverse Event (TEAE)</title>
        <description>A TEAE was defined as an adverse event that emerged during treatment, having been absent at pretreatment or reemerged during treatment, having been present at pretreatment but stopped before treatment, or worsened in severity during treatment relative to the pretreatment state, when the adverse event is continuous. An adverse event was defined as any untoward medical occurrence in a participant administered an investigational product.</description>
        <time_frame>From date of first dose up to 28 days after the last dose of study treatment (up to 7.5 months)</time_frame>
        <population>SAS included all participants who received at least one dose of study drug (Lenvatinib or Everolimus).</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 2: Cohort 1, Ewing Sarcoma</title>
            <description>Participants with recurrent or refractory ewing sarcoma received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily for up to 7 cycles (each cycle was 28 days) unless participant discontinued early from the study.</description>
          </group>
          <group group_id="O2">
            <title>Phase 2: Cohort 2, Rhabdomyosarcoma</title>
            <description>Participants with recurrent or refractory rhabdomyosarcoma received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily for up to 7 cycles (each cycle was 28 days) unless participant discontinued early from the study.</description>
          </group>
          <group group_id="O3">
            <title>Phase 2: Cohort 3, HGG</title>
            <description>Participants with recurrent or refractory HGG received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily for up to 7 cycles (each cycle was 28 days) unless participant discontinued early from the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 2: Number of Participants With Any Treatment-emergent Adverse Event (TEAE)</title>
          <description>A TEAE was defined as an adverse event that emerged during treatment, having been absent at pretreatment or reemerged during treatment, having been present at pretreatment but stopped before treatment, or worsened in severity during treatment relative to the pretreatment state, when the adverse event is continuous. An adverse event was defined as any untoward medical occurrence in a participant administered an investigational product.</description>
          <population>SAS included all participants who received at least one dose of study drug (Lenvatinib or Everolimus).</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="10"/>
                <count group_id="O2" value="20"/>
                <count group_id="O3" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                    <measurement group_id="O2" value="19"/>
                    <measurement group_id="O3" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase 2: Number of Participants With Any Treatment-emergent Serious Adverse Event (TESAE)</title>
        <description>A TESAE was any untoward medical occurrence that at any dose: resulted in death; life threatening condition; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect or was medically important due to other reasons than the above mentioned criteria. An adverse event was defined as any untoward medical occurrence in a participant administered an investigational product.</description>
        <time_frame>From date of first dose up to 28 days after the last dose of study treatment (up to 7.5 months)</time_frame>
        <population>SAS included all participants who received at least one dose of study drug (Lenvatinib or Everolimus).</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 2: Cohort 1, Ewing Sarcoma</title>
            <description>Participants with recurrent or refractory ewing sarcoma received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily for up to 7 cycles (each cycle was 28 days) unless participant discontinued early from the study.</description>
          </group>
          <group group_id="O2">
            <title>Phase 2: Cohort 2, Rhabdomyosarcoma</title>
            <description>Participants with recurrent or refractory rhabdomyosarcoma received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily for up to 7 cycles (each cycle was 28 days) unless participant discontinued early from the study.</description>
          </group>
          <group group_id="O3">
            <title>Phase 2: Cohort 3, HGG</title>
            <description>Participants with recurrent or refractory HGG received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily for up to 7 cycles (each cycle was 28 days) unless participant discontinued early from the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 2: Number of Participants With Any Treatment-emergent Serious Adverse Event (TESAE)</title>
          <description>A TESAE was any untoward medical occurrence that at any dose: resulted in death; life threatening condition; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect or was medically important due to other reasons than the above mentioned criteria. An adverse event was defined as any untoward medical occurrence in a participant administered an investigational product.</description>
          <population>SAS included all participants who received at least one dose of study drug (Lenvatinib or Everolimus).</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="10"/>
                <count group_id="O2" value="20"/>
                <count group_id="O3" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="8"/>
                    <measurement group_id="O3" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From date of first dose up to 28 days after the last dose of study treatment (Phase 1: Up to 17.5 months; Phase 2: Up to 7.5 months)</time_frame>
      <desc>SAS included all participants who received at least 1 dose of study drug (lenvatinib or everolimus).</desc>
      <group_list>
        <group group_id="E1">
          <title>Phase 1: Lenvatinib 8 mg/m^2 + Everolimus 3 mg/m^2</title>
          <description>Participants with recurrent or refractory solid tumors received lenvatinib 8 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily in cycle 1 (each cycle was 28 days) until the occurrence of PD, clinical benefit, development of unacceptable toxicity leading to withdrawal from the study, study discontinuation or for a maximum of 18 cycles (each cycle was 28 days) whichever occurred first.</description>
        </group>
        <group group_id="E2">
          <title>Phase 1: Lenvatinib 11 mg/m^2 + Everolimus 3 mg/m^2</title>
          <description>Participants with recurrent or refractory solid tumors received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily in cycle 1 (each cycle was 28 days) until the occurrence of PD, clinical benefit, development of unacceptable toxicity leading to withdrawal from the study, study discontinuation or for a maximum of 18 cycles (each cycle was 28 days) whichever occurred first.</description>
        </group>
        <group group_id="E3">
          <title>Phase 2: Cohort 1, Ewing Sarcoma</title>
          <description>Participants with recurrent or refractory ewing sarcoma received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily for up to 7 cycles (each cycle was 28 days) unless participant discontinued early from the study.</description>
        </group>
        <group group_id="E4">
          <title>Phase 2: Cohort 2, Rhabdomyosarcoma</title>
          <description>Participants with recurrent or refractory rhabdomyosarcoma received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily for up to 7 cycles (each cycle was 28 days) unless participant discontinued early from the study.</description>
        </group>
        <group group_id="E5">
          <title>Phase 2: Cohort 3, HGG</title>
          <description>Participants with recurrent or refractory HGG received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily for up to 7 cycles (each cycle was 28 days) unless participant discontinued early from the study.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 25.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="18"/>
                <counts group_id="E3" subjects_affected="9" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="17" subjects_at_risk="20"/>
                <counts group_id="E5" subjects_affected="8" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="18"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="8" subjects_at_risk="20"/>
                <counts group_id="E5" subjects_affected="8" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Febrile neutropenia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Hypothyroidism</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Eyelid oedema</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Mouth haemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Oral cavity fistula</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Pancreatitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Pneumatosis intestinalis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Face oedema</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="10"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Pneumonia aspiration</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infections</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Tendon rupture</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Hypophosphataemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Musculoskeletal pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Muscular weakness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Musculoskeletal chest pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Malignant pleural effusion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Tumour haemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Cancer pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dysarthria</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Nystagmus</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Seizure</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Cerebrospinal fluid leakage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Depressed level of consciousness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Encephalopathy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Hydrocephalus</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Optic neuritis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Paraesthesia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Mental status changes</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="18"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Pneumothorax</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Respiratory failure</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Haemothorax</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Deep vein thrombosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 25.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="18" subjects_at_risk="18"/>
                <counts group_id="E3" subjects_affected="10" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="19" subjects_at_risk="20"/>
                <counts group_id="E5" subjects_affected="11" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" events="6" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E2" events="16" subjects_affected="6" subjects_at_risk="18"/>
                <counts group_id="E3" events="17" subjects_affected="5" subjects_at_risk="10"/>
                <counts group_id="E4" events="10" subjects_affected="7" subjects_at_risk="20"/>
                <counts group_id="E5" events="5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Lymphopenia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Sinus bradycardia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="3" subjects_affected="3" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Bradycardia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Sinus tachycardia</sub_title>
                <counts group_id="E1" events="6" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E2" events="5" subjects_affected="4" subjects_at_risk="18"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="5" subjects_affected="3" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Tachycardia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Wolff-Parkinson-White syndrome</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Ear pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperthyroidism</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Hypothyroidism</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E2" events="13" subjects_affected="10" subjects_at_risk="18"/>
                <counts group_id="E3" events="3" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E4" events="14" subjects_affected="8" subjects_at_risk="20"/>
                <counts group_id="E5" events="7" subjects_affected="6" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Hyperparathyroidism</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Dry eye</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Miosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Eye pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Vision blurred</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal distension</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="5"/>
                <counts group_id="E2" events="16" subjects_affected="9" subjects_at_risk="18"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="10" subjects_affected="7" subjects_at_risk="20"/>
                <counts group_id="E5" events="5" subjects_affected="4" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Anal incontinence</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Aphthous ulcer</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Cheilitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="4" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E2" events="4" subjects_affected="3" subjects_at_risk="18"/>
                <counts group_id="E3" events="5" subjects_affected="4" subjects_at_risk="10"/>
                <counts group_id="E4" events="8" subjects_affected="6" subjects_at_risk="20"/>
                <counts group_id="E5" events="3" subjects_affected="3" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="10" subjects_affected="3" subjects_at_risk="5"/>
                <counts group_id="E2" events="23" subjects_affected="10" subjects_at_risk="18"/>
                <counts group_id="E3" events="10" subjects_affected="5" subjects_at_risk="10"/>
                <counts group_id="E4" events="11" subjects_affected="8" subjects_at_risk="20"/>
                <counts group_id="E5" events="9" subjects_affected="7" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Gingival pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Mouth haemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="9" subjects_affected="4" subjects_at_risk="5"/>
                <counts group_id="E2" events="8" subjects_affected="5" subjects_at_risk="18"/>
                <counts group_id="E3" events="4" subjects_affected="3" subjects_at_risk="10"/>
                <counts group_id="E4" events="14" subjects_affected="9" subjects_at_risk="20"/>
                <counts group_id="E5" events="5" subjects_affected="4" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Oral pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="3" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Stomatitis</sub_title>
                <counts group_id="E1" events="10" subjects_affected="4" subjects_at_risk="5"/>
                <counts group_id="E2" events="8" subjects_affected="5" subjects_at_risk="18"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E4" events="21" subjects_affected="9" subjects_at_risk="20"/>
                <counts group_id="E5" events="3" subjects_affected="2" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Toothache</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="10" subjects_affected="3" subjects_at_risk="5"/>
                <counts group_id="E2" events="20" subjects_affected="11" subjects_at_risk="18"/>
                <counts group_id="E3" events="7" subjects_affected="3" subjects_at_risk="10"/>
                <counts group_id="E4" events="11" subjects_affected="7" subjects_at_risk="20"/>
                <counts group_id="E5" events="10" subjects_affected="7" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Pancreatitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="3" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Flatulence</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="5"/>
                <counts group_id="E2" events="9" subjects_affected="6" subjects_at_risk="18"/>
                <counts group_id="E3" events="7" subjects_affected="6" subjects_at_risk="10"/>
                <counts group_id="E4" events="16" subjects_affected="11" subjects_at_risk="20"/>
                <counts group_id="E5" events="5" subjects_affected="3" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Influenza like illness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Localised oedema</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="7" subjects_affected="5" subjects_at_risk="18"/>
                <counts group_id="E3" events="8" subjects_affected="4" subjects_at_risk="10"/>
                <counts group_id="E4" events="4" subjects_affected="3" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" events="7" subjects_affected="3" subjects_at_risk="5"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="7" subjects_affected="3" subjects_at_risk="18"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="8" subjects_affected="5" subjects_at_risk="20"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Peripheral swelling</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Face oedema</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Gait disturbances</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertransaminasaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Steatohepatitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Contrast media allergy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Conjunctivitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Device related infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Oral candidiasis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Otitis media</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Pharyngitis</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Skin infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infections</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="3" subjects_affected="3" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Vulvovaginal mycotic infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Otitis media acute</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Rash pustular</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="2" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Respiratory tract infection viral</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Allergic transfusion reaction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="2" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Stoma site pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Tendon rupture</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Wrist fracture</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Procedural pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Wound complication</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Wound dehiscence</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="10" subjects_affected="5" subjects_at_risk="18"/>
                <counts group_id="E3" events="7" subjects_affected="3" subjects_at_risk="10"/>
                <counts group_id="E4" events="7" subjects_affected="7" subjects_at_risk="20"/>
                <counts group_id="E5" events="4" subjects_affected="3" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Amylase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="13" subjects_affected="5" subjects_at_risk="18"/>
                <counts group_id="E3" events="6" subjects_affected="4" subjects_at_risk="10"/>
                <counts group_id="E4" events="13" subjects_affected="8" subjects_at_risk="20"/>
                <counts group_id="E5" events="5" subjects_affected="4" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Blood alkaline phosphatase increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E5" events="3" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Blood cholesterol increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="23" subjects_affected="6" subjects_at_risk="18"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E4" events="14" subjects_affected="11" subjects_at_risk="20"/>
                <counts group_id="E5" events="12" subjects_affected="4" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Blood creatinine increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="4" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Blood thyroid stimulating hormone increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="3" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Blood fibrinogen decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Blood lactate dehydrogenase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="3" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Ejection fraction decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Electrocardiogram QT prolonged</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Haemoglobin increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="4" subjects_affected="3" subjects_at_risk="18"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="9" subjects_affected="3" subjects_at_risk="20"/>
                <counts group_id="E5" events="5" subjects_affected="3" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Gamma-glutamyltransferase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>International normalised ratio increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Lipase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="6" subjects_affected="4" subjects_at_risk="20"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" events="14" subjects_affected="3" subjects_at_risk="5"/>
                <counts group_id="E2" events="13" subjects_affected="6" subjects_at_risk="18"/>
                <counts group_id="E3" events="27" subjects_affected="8" subjects_at_risk="10"/>
                <counts group_id="E4" events="32" subjects_affected="11" subjects_at_risk="20"/>
                <counts group_id="E5" events="10" subjects_affected="2" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" events="6" subjects_affected="3" subjects_at_risk="5"/>
                <counts group_id="E2" events="12" subjects_affected="4" subjects_at_risk="18"/>
                <counts group_id="E3" events="7" subjects_affected="3" subjects_at_risk="10"/>
                <counts group_id="E4" events="14" subjects_affected="7" subjects_at_risk="20"/>
                <counts group_id="E5" events="9" subjects_affected="2" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" events="6" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E2" events="22" subjects_affected="7" subjects_at_risk="18"/>
                <counts group_id="E3" events="9" subjects_affected="5" subjects_at_risk="10"/>
                <counts group_id="E4" events="21" subjects_affected="10" subjects_at_risk="20"/>
                <counts group_id="E5" events="4" subjects_affected="3" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Platelet count increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>SARS-CoV-2 test positive</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E2" events="12" subjects_affected="6" subjects_at_risk="18"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="10" subjects_affected="6" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Weight increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="3" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>White blood cell count decreased</sub_title>
                <counts group_id="E1" events="7" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E2" events="16" subjects_affected="6" subjects_at_risk="18"/>
                <counts group_id="E3" events="17" subjects_affected="6" subjects_at_risk="10"/>
                <counts group_id="E4" events="24" subjects_affected="8" subjects_at_risk="20"/>
                <counts group_id="E5" events="8" subjects_affected="2" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" events="7" subjects_affected="4" subjects_at_risk="5"/>
                <counts group_id="E2" events="5" subjects_affected="4" subjects_at_risk="18"/>
                <counts group_id="E3" events="3" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E4" events="9" subjects_affected="6" subjects_at_risk="20"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E2" events="5" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="5" subjects_affected="4" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Hyperglycaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="5" subjects_affected="4" subjects_at_risk="18"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E4" events="6" subjects_affected="4" subjects_at_risk="20"/>
                <counts group_id="E5" events="7" subjects_affected="3" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Hypercalcaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Hypercholesterolaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Hyperkalaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="4" subjects_affected="4" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Hypermagnesaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E3" events="4" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E4" events="6" subjects_affected="3" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Hypertriglyceridaemia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E2" events="51" subjects_affected="11" subjects_at_risk="18"/>
                <counts group_id="E3" events="18" subjects_affected="5" subjects_at_risk="10"/>
                <counts group_id="E4" events="26" subjects_affected="12" subjects_at_risk="20"/>
                <counts group_id="E5" events="22" subjects_affected="6" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Hypoalbuminaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="9" subjects_affected="4" subjects_at_risk="18"/>
                <counts group_id="E3" events="13" subjects_affected="5" subjects_at_risk="10"/>
                <counts group_id="E4" events="14" subjects_affected="4" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Hypocalcaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="18"/>
                <counts group_id="E3" events="7" subjects_affected="5" subjects_at_risk="10"/>
                <counts group_id="E4" events="6" subjects_affected="4" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Hypocholesterolaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E3" events="6" subjects_affected="4" subjects_at_risk="10"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E5" events="2" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Hypomagnesaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="3" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="7" subjects_affected="6" subjects_at_risk="18"/>
                <counts group_id="E3" events="15" subjects_affected="7" subjects_at_risk="10"/>
                <counts group_id="E4" events="3" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Hypophosphataemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="6" subjects_affected="3" subjects_at_risk="18"/>
                <counts group_id="E3" events="14" subjects_affected="8" subjects_at_risk="10"/>
                <counts group_id="E4" events="10" subjects_affected="6" subjects_at_risk="20"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Hypernatraemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Hyperphosphataemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Hypoglycaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="3" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E3" events="5" subjects_affected="3" subjects_at_risk="10"/>
                <counts group_id="E4" events="11" subjects_affected="6" subjects_at_risk="20"/>
                <counts group_id="E5" events="5" subjects_affected="3" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="6" subjects_affected="4" subjects_at_risk="20"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Muscular weakness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="5"/>
                <counts group_id="E2" events="5" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E3" events="5" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="6" subjects_affected="4" subjects_at_risk="20"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Neck pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="5" subjects_affected="3" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="9" subjects_affected="4" subjects_at_risk="18"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E4" events="7" subjects_affected="5" subjects_at_risk="20"/>
                <counts group_id="E5" events="3" subjects_affected="2" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Bone pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Joint range of motion decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Musculoskeletal pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Myositis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="4" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Periostitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Pain in jaw</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Spinal pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Fibrous cortical defect</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Tumour haemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Tumour pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Cancer pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="3" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E4" events="3" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Malignant pleural effusion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Ataxia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Dysarthria</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="3" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="14" subjects_affected="3" subjects_at_risk="5"/>
                <counts group_id="E2" events="10" subjects_affected="8" subjects_at_risk="18"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="5" subjects_affected="5" subjects_at_risk="20"/>
                <counts group_id="E5" events="7" subjects_affected="5" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Hydrocephalus</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Hypersomnia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Lethargy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Seizure</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Tremor</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Intracranial haematoma</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Haemorrhage intracranial</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Product Issues</title>
            <event_list>
              <event>
                <sub_title>Device dislocation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E4" events="4" subjects_affected="4" subjects_at_risk="20"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Agitation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="3" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Irritability</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Restlessness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E2" events="4" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Proteinuria</sub_title>
                <counts group_id="E1" events="4" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="37" subjects_affected="8" subjects_at_risk="18"/>
                <counts group_id="E3" events="15" subjects_affected="8" subjects_at_risk="10"/>
                <counts group_id="E4" events="23" subjects_affected="10" subjects_at_risk="20"/>
                <counts group_id="E5" events="4" subjects_affected="4" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Haematuria</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E3" events="5" subjects_affected="4" subjects_at_risk="10"/>
                <counts group_id="E4" events="6" subjects_affected="6" subjects_at_risk="20"/>
                <counts group_id="E5" events="3" subjects_affected="3" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Dysuria</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Micturition urgency</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Pollakiuria</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Urinary incontinence</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Urinary retention</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Urinary tract pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Glycosuria</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Renal tubular dysfunction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Pelvic pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Atelectasis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="7" subjects_affected="4" subjects_at_risk="18"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="5" subjects_affected="4" subjects_at_risk="20"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Dysphonia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="4" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E4" events="5" subjects_affected="4" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="9" subjects_affected="6" subjects_at_risk="20"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Hiccups</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E3" events="3" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="5" subjects_affected="5" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="18"/>
                <counts group_id="E3" events="3" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E4" events="12" subjects_affected="7" subjects_at_risk="20"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E3" events="5" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Pneumothorax</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Productive cough</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Rhinitis allergic</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Rhinorrhoea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Tachypnoea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="4" subjects_affected="3" subjects_at_risk="18"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="4" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Pulmonary oedema</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Respiratory distress</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Dermatitis acneiform</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Dermatitis contact</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="6" subjects_affected="4" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Hyperhidrosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Palmar-plantar erythrodysaesthesia syndrome</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E4" events="5" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E5" events="5" subjects_affected="2" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="4" subjects_affected="3" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="6" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="4" subjects_affected="3" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Scab</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Skin atrophy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Skin ulcer</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="4" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Urticaria</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Petechiae</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="3" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Erythemas</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Pain of skin</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hot flush</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="14" subjects_affected="4" subjects_at_risk="5"/>
                <counts group_id="E2" events="19" subjects_affected="13" subjects_at_risk="18"/>
                <counts group_id="E3" events="4" subjects_affected="3" subjects_at_risk="10"/>
                <counts group_id="E4" events="18" subjects_affected="10" subjects_at_risk="20"/>
                <counts group_id="E5" events="5" subjects_affected="4" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Eisai Medical Information</name_or_title>
      <organization>Eisai Inc.</organization>
      <phone>1-888-274-2378</phone>
      <email>esi_oncmedinfo@eisai.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03245151
org study id: E7080-A001-216
nct id: NCT03245151
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
Phase 1 of this study, utilizing a rolling 6 design, will be conducted to determine a maximum
      tolerated dose (MTD) and recommended Phase 2 dose (RP2D), and to describe the toxicities of
      lenvatinib administered in combination with everolimus once daily to pediatric participants
      with recurrent/refractory solid tumors. Phase 2, utilizing Simon's optimal 2-stage design,
      will be conducted to estimate the antitumor activity of lenvatinib in combination with
      everolimus in pediatric participants with selected recurrent/refractory solid tumors
      including Ewing sarcoma, rhabdomyosarcoma, and high grade glioma (HGG) using objective
      response rate (ORR) at Week 16 as the outcome measure.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Phase 1: Maximum Tolerated Dose (MTD) of Lenvatinib in Combination With Everolimus
time frame: Cycle 1 (Each cycle was of 28 days)
description: MTD was defined as the highest dose level at which no more than 1/6 participants experienced a dose limiting toxicity (DLTs), with the next higher dose having at least 0 of 3 or 1 of 6 participants experiencing DLTs. DLT was graded according to common terminology criteria for adverse events (CTCAE) version 4.03.
measure: Phase 1: Recommended Phase 2 Dose (RP2D) of Lenvatinib in Combination With Everolimus
time frame: Cycle 1 (Each cycle was of 28 days)
description: The RP2D of lenvatinib in combination with everolimus was determined by Dose Escalation Committee (DEC) based on safety (including DLTs), pharmacokinetic and clinical data. DLT was graded according to CTCAE v4.03.
measure: Phase 1: Number of Participants With Any Treatment-emergent Adverse Event (TEAE)
time frame: From date of first dose up to 28 days after the last dose of study treatment (Up to 17.5 months)
description: A TEAE was defined as an adverse event that emerged during treatment, having been absent at pretreatment or reemerged during treatment, having been present at pretreatment but stopped before treatment, or worsened in severity during treatment relative to the pretreatment state, when the adverse event is continuous. An adverse event was defined as any untoward medical occurrence in a participant administered an investigational product.
measure: Phase 1: Number of Participants With Any Treatment-emergent Serious Adverse Event (TESAE)
time frame: From date of first dose up to 28 days after the last dose of study treatment (Up to 17.5 months)
description: A TESAE was any untoward medical occurrence that at any dose: resulted in death; life threatening condition; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect or was medically important due to other reasons than the above mentioned criteria. An adverse event was defined as any untoward medical occurrence in a participant administered an investigational product.
measure: Phase 2: Objective Response Rate (ORR) at Week 16
time frame: Week 16
description: ORR at Week 16 was defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) at Week 16 based on investigator assessment according to response evaluation criteria in solid tumors (RECIST) version 1.1 for non-HGG cohorts and response assessment in neuro-oncology (RANO) for HGG cohort. CR was defined as disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis less than (<) 10 millimeter (mm). PR was defined as at least a 30 percent (%) decrease in the sum of diameter (SOD) of target lesions, taking as reference the baseline sum diameters.
measure: Phase 1: Objective Response Rate (ORR)
time frame: From the date of the first dose of study drug to the date of first documentation of disease progression or death, whichever occurred first (up to 16.5 months)
description: ORR was defined as the percentage of participants with BOR of CR or PR based on investigator assessment according to RECIST version 1.1 for non-HGG cohorts and RANO for HGG cohort. CR was defined as disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis <10 mm. PR was defined as at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters.
measure: Phase 2: Objective Response Rate (ORR)
time frame: From the date of the first dose of study drug to the date of first documentation of disease progression or death, which ever occurred first (up to 6.5 months)
description: ORR was defined as the percentage of participants with BOR of CR or PR based on investigator assessment according to RECIST version 1.1 for non-HGG cohorts and RANO for HGG cohort. CR was defined as disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis <10 mm. PR was defined as at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters.
measure: Phase 1: Disease Control Rate (DCR)
time frame: From first dose of study drug until PD or death, whichever occurred first (up to 16.5 months)
description: DCR was defined as percentage of participants with a confirmed CR, PR, or stable disease (SD) (SD duration >=7 weeks since the first dose of study treatment) divided by number of participants in analysis set. DCR was assessed by an investigator based on RECIST v1.1 for non-HGG participants or RANO for HGG participants. CR: disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis <10 mm. PR: at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SOD. PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.
measure: Phase 2: Disease Control Rate (DCR)
time frame: From first dose of study drug until PD or death, whichever occurred first (up to 6.5 months)
description: DCR was defined as percentage of participants with confirmed CR, PR, or SD (SD duration greater than or equal to [>=] 7 weeks since first dose of study treatment) divided by number of participants in analysis set. DCR was assessed by investigator based on RECIST v1.1 for non-HGG cohorts or RANO for HGG cohort. CR: disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis <10 mm. PR: at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SOD. PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.
measure: Phase 1: Clinical Benefit Rate (CBR)
time frame: From first dose of study drug until PD or death, whichever occurred first (up to 16.5 months)
description: CBR was defined as percentage of participants who had BOR of CR, PR, or durable SD (SD duration >=23 weeks since the first dose of study treatment) divided by number of participants in analysis set. CBR was assessed by an investigator based on RECIST v1.1 for non-HGG participants or RANO for HGG participants. CR: disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis <10 mm. PR: at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SOD. PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.
measure: Phase 2: Clinical Benefit Rate (CBR)
time frame: From first dose of study drug until PD or death, whichever occurred first (up to 6.5 months)
description: CBR was defined as percentage of participants who had BOR of CR, PR, or durable SD (SD duration >=23 weeks since the first dose of study treatment) divided by number of participants in analysis set. CBR was assessed by an investigator based on RECIST v1.1 for non-HGG cohorts or RANO for HGG cohort. CR: disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis <10 mm. PR: at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SOD. PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.
measure: Phase 1: Duration of Response (DOR)
time frame: From date of the first observation of CR or PR until the date of first observation of progression or date of death (up to 16.5 months)
description: DOR was defined as the time (in months) from the date of first observation of confirmed response (PR or CR) to the date of the first observation of progression based on the investigator's assessment utilizing RECIST 1.1 for non-HGG cohorts and RANO for HGG cohorts, or date of death, whatever the cause. CR: disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis <10 mm. PR: at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. PD was defined as at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.
measure: Phase 2: Duration of Response (DOR)
time frame: From date of the first observation of CR or PR until the date of first observation of progression or date of death (up to 6.5 months)
description: DOR was defined as the time (in months) from the date of first observation of confirmed response (PR or CR) to the date of the first observation of progression based on the investigator's assessment utilizing RECIST 1.1 for non-HGG cohorts and RANO for HGG cohort, or date of death, whatever the cause. CR: disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis <10 mm. PR: at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. PD was defined as at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.
measure: Phase 1: Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration of Lenvatinib (AUC[0-t Hours])
time frame: Cycle 1 Days 1 and 15: 0-8 hours post-dose (Cycle length=28 days)
description: AUC0-t of lenvatinib was quantified using validated liquid chromatography tandem mass spectrometry (LC-MS/MS) methods.
measure: Phase 1: Maximum Plasma Concentration of Lenvatinib (Cmax)
time frame: Cycle 1 Days 1 and 15: 0-8 hours post-dose (Cycle length=28 days)
description: Cmax of lenvatinib was quantified using validated liquid LC-MS/MS methods.
measure: Phase 1: Time to Reach Maximum Plasma Concentration (Cmax) of Lenvatinib (Tmax)
time frame: Cycle 1 Days 1 and 15: 0-8 hours post-dose (Cycle length=28 days)
description: Tmax of lenvatinib was quantified using validated liquid LC-MS/MS methods.
measure: Phase 1: Trough Concentrations (Ctrough) of Everolimus When Administered in Combination With Lenvatinib
time frame: Cycle 1 Days 1, 2, 15 and 22: Pre-dose (Cycle length=28 days)
description: Trough concentrations of everolimus was quantified using validated liquid LC-MS/MS methods.
measure: Phase 2: Number of Participants With Any Treatment-emergent Adverse Event (TEAE)
time frame: From date of first dose up to 28 days after the last dose of study treatment (up to 7.5 months)
description: A TEAE was defined as an adverse event that emerged during treatment, having been absent at pretreatment or reemerged during treatment, having been present at pretreatment but stopped before treatment, or worsened in severity during treatment relative to the pretreatment state, when the adverse event is continuous. An adverse event was defined as any untoward medical occurrence in a participant administered an investigational product.
measure: Phase 2: Number of Participants With Any Treatment-emergent Serious Adverse Event (TESAE)
time frame: From date of first dose up to 28 days after the last dose of study treatment (up to 7.5 months)
description: A TESAE was any untoward medical occurrence that at any dose: resulted in death; life threatening condition; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect or was medically important due to other reasons than the above mentioned criteria. An adverse event was defined as any untoward medical occurrence in a participant administered an investigational product.
arm group label: Phase 1: Phase 1; Recurrent or refractory solid tumors
arm group type: Experimental
description: During Phase 1 (Treatment Phase: 1 cycle; 28 days of treatment), utilizing a rolling 6 design, participants with recurrent or refractory solid tumors will receive escalating doses of lenvatinib in combination with everolimus for determination of the maximum tolerated dose (MTD) and the recommended Phase 2 dose (RP2D). Participants who complete 1 cycle of treatment will transition to the Extension Phase, in which they will continue to receive the same study treatment in 28-day cycles.
arm group label: Phase 2: Cohort 1, Ewing sarcoma
arm group type: Experimental
description: During Phase 2 (four 28-day cycles [up to 16 weeks of treatment]), utilizing Simon's optimal 2-stage design, participants with recurrent or refractory Ewing sarcoma (Cohort 1) will receive the RP2D of lenvatinib in combination with everolimus determined in Phase 1. Participants who discontinue study treatment before completing 4 cycles will transition to the Off-treatment Visit. Participants who complete 4 cycles will transition to the Extension Phase, in which they will continue to receive the same study treatment in 28-day cycles.
arm group label: Phase 2: Cohort 2, Rhabdomyosarcoma
arm group type: Experimental
description: During Phase 2 (four 28-day cycles [up to 16 weeks of treatment]), utilizing Simon's optimal 2-stage design, participants with recurrent or refractory rhabdomyosarcoma (Cohort 2) will receive the RP2D of lenvatinib in combination with everolimus determined in Phase 1 (1 cycle; 4 weeks of treatment). Participants who discontinue study treatment before completing 4 cycles will transition to the Off-treatment Visit. Participants who complete 4 cycles will transition to the Extension Phase, in which they will continue to receive the same study treatment in 28-day cycles.
arm group label: Phase 2: Cohort 3, High Grade Glioma (HGG)
arm group type: Experimental
description: During Phase 2 (four 28-day cycles [up to 16 weeks of treatment]), utilizing Simon's optimal 2-stage design, participants with recurrent or refractory HGG (Cohort 3) will receive the RP2D of lenvatinib in combination with everolimus determined in Phase 1 (1 cycle; 4 weeks). Participants who discontinue study treatment before completing 4 cycles will transition to the Off-treatment Visit. Participants who complete 4 cycles will transition to the Extension Phase, in which they will continue to receive the same study treatment in 28-day cycles.
intervention type: Drug
intervention name: Lenvatinib
description: oral hard capsules containing 1 mg, 4 mg, or 10 mg lenvatinib, or an extemporaneous suspension
arm group label: Phase 1: Phase 1; Recurrent or refractory solid tumors
arm group label: Phase 2: Cohort 1, Ewing sarcoma
arm group label: Phase 2: Cohort 2, Rhabdomyosarcoma
arm group label: Phase 2: Cohort 3, High Grade Glioma (HGG)
intervention type: Drug
intervention name: Everolimus
description: 2 mg, 3 mg, or 5 mg tablets for oral suspension
arm group label: Phase 1: Phase 1; Recurrent or refractory solid tumors
arm group label: Phase 2: Cohort 1, Ewing sarcoma
arm group label: Phase 2: Cohort 2, Rhabdomyosarcoma
arm group label: Phase 2: Cohort 3, High Grade Glioma (HGG)
criteria: 
gender: All
minimum age: 2 Years
maximum age: 21 Years
healthy volunteers: No
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country: Canada
country: United States
country: Palau
responsible party type: Sponsor
mesh term: Central Nervous System Neoplasms
mesh term: Recurrence
mesh term: Everolimus
mesh term: Lenvatinib
provided document: 
provided document: 
participant flow: 
baseline: 
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reported events: 
certain agreements: 
point of contact: 