<clinical_study>
  <!-- This xml conforms to an XML Schema at:
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  <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/NCT01713946</url>
  </required_header>
  <id_info>
    <org_study_id>CRAD001M2304</org_study_id>
    <secondary_id>2011-000860-90</secondary_id>
    <nct_id>NCT01713946</nct_id>
  </id_info>
  <brief_title>A Placebo-controlled Study of Efficacy &amp; Safety of 2 Trough-ranges of Everolimus as Adjunctive Therapy in Patients With Tuberous Sclerosis Complex (TSC) &amp; Refractory Partial-onset Seizures</brief_title>
  <acronym>EXIST-3</acronym>
  <official_title>A Three-arm, Randomized, Double-blind, Placebo-controlled Study of the Efficacy and Safety of Two Trough-ranges of Everolimus as Adjunctive Therapy in Patients With Tuberous Sclerosis Complex (TSC) Who Have Refractory Partial-onset Seizures</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Novartis Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Novartis</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study evaluated the efficacy and safety of two trough-ranges of everolimus given as&#xD;
      adjunctive therapy in patients with tuberous sclerosis complex (TSC) who had refractory&#xD;
      partial-onset seizures.&#xD;
&#xD;
      The study consisted of 4 phases for each patient Baseline phase:[From Screening Week -8 (V1)&#xD;
      to randomization visit at Week 0 (V2)], Core phase [from randomization at Week 0 (V2) to Week&#xD;
      18 (V11)], Extension phase [from Week 18 (V11) until 48 weeks after the last patient had&#xD;
      completed the core phase] and Post Extension phase [from end of Extension phase to end of&#xD;
      study].&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 29, 2013</start_date>
  <completion_date type="Actual">October 25, 2017</completion_date>
  <primary_completion_date type="Actual">October 25, 2017</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Core Phase: European Medicine Agency (EMA): Seizure Frequency Response Rate</measure>
    <time_frame>Baseline (8-week period before randomization), Week 7 to 18 (12-week maintenance period of the core phase)</time_frame>
    <description>Comparison of response rates in the everolimus low-trough treatment arm (3-7 ng/mL), high-trough treatment arm (9-15 ng/mL) and placebo arm. Response means at least a 50% reduction from baseline in partial-onset seizure frequency during the maintenance period of the core phase.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Core Phase: Food &amp; Drug Administration (FDA): Percentage Change From Baseline in Partial Onset-seizure Frequency</measure>
    <time_frame>Baseline (8-week period before randomization), Week 7 to 18 (12-week maintenance period of the core phase)</time_frame>
    <description>Comparison of median percent change from baseline in weekly seizure frequency in the everolimus low-trough treatment arm (3-7 ng/mL), high-trough treatment arm (9-15 ng/mL) and placebo arm during maintenance period of the core phase. Percentage change from baseline in average weekly seizure frequency during the maintenance period of the Core phase (SFcfb) = 100 × (SFB - SFM) ÷ SFB where:&#xD;
SFB is the average weekly seizure frequency in the Baseline phase SFM is the average weekly seizure frequency in the maintenance period of the Core phase A positive percentage change from baseline (SFcfb) means a reduction in seizure frequency whereas a negative percentage change from baseline (SFcfb) means an increase in seizure frequency.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Seizure-free Patients During the Maintenance Period of the Core Phase</measure>
    <time_frame>Baseline (8-week period before randomization), Week 7 to 18 (12-week maintenance period of the core phase)</time_frame>
    <description>Comparison of seizure freedom (100% reduction in seizure frequency) in the everolimus low-trough treatment arm (3-7 ng/mL), high-trough treatment arm (9-15 ng/mL) and placebo arm during maintenance period of the core phase. Seizure free means a 100% reduction from baseline in partial-onset seizure frequency during maintenance period of the core phase.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Core Phase: Percentage of Patients With at Least a 25% Reduction in Seizure Frequency</measure>
    <time_frame>Baseline (8-week period before randomization), Week 7 to 18 (12-week maintenance period of the core phase)</time_frame>
    <description>Comparison of percentage of patients with at least ≥ 25% reduction in seizure frequency in the everolimus low-trough treatment arm (3-7 ng/mL), high-trough treatment arm (9-15 ng/mL) and placebo arm during maintenance period of the core phase. At least 25% reduction from baseline in partial-onset seizure frequency during maintenance period of the core phase.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Core Phase: Distribution of Reduction From Baseline in Seizure Frequency</measure>
    <time_frame>Baseline (8-week period before randomization), Week 7 to 18 (12-week maintenance period of the core phase)</time_frame>
    <description>Comparison of percentage of patients in six categories of seizure reduction from baseline (≤ -25% (exacerbation); &gt; -25% to &lt; 25% (no change); ≥ 25% to &lt; 50%; ≥ 50% to &lt; 75%; ≥ 75% to &lt; 100%; 100% (seizure-freedom)) in the everolimus low-trough treatment arm (3-7 ng/mL), high-trough treatment arm (9-15 ng/mL) and placebo arm during maintenance period of the core phase</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Core Phase: Changes From Baseline in Number of Seizure-free Days</measure>
    <time_frame>Baseline (8-week period before randomization), Week 7 to 18 (12-week maintenance period of the core phase)</time_frame>
    <description>Comparison of seizure-free days relative to baseline in the everolimus low-trough treatment arm (3-7 ng/mL), high-trough treatment arm (9-15 ng/mL) and placebo arm during maintenance period of the core phase</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Core Phase: Probability That a Patient Remains On-treatment up to a Specified Time Point</measure>
    <time_frame>Week 6, Week 12, Week 18</time_frame>
    <description>Comparison of time to treatment discontinuation in the everolimus low-trough treatment arm (3-7 ng/mL), high-trough treatment arm (9-15 ng/mL) and placebo arm during the core phase. Treatment duration is defined as the time from randomization until the date of permanent study treatment discontinuation (for any reason) at any time during the Core phase.&#xD;
The percentage event-free probability estimate is the estimated probability that a patient will remain on-treatment up to a specified time point (Week 6, 12, 18)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Core Phase: Change From Baseline in the QOLCE Overall Quality-of-life Score for Patients &lt;11 Years</measure>
    <time_frame>Baseline, Week 18</time_frame>
    <description>Comparison of quality of life in the everolimus (from 3 age specific questionnaires) low-trough treatment arm (3-7 ng/mL), high-trough treatment arm (9-15 ng/mL) and placebo arm at the end of the core phase. The Quality of Life Childhood Epilepsy (QOLCE) questionnaire, used for patients &lt; 11 years at baseline, was completed by the patient's parent or caregiver. It consists of 16 subscales (13 multi-item scales and 3 single item scales) and one overall quality-of-life score. Scores range from 0-100, with higher scores corresponding to improved QoL. The Overall Quality of Life Score is computed by adding each subscale score for each individual and then dividing by 16.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Core Phase: Change From Baseline in the QOLIE-AD-48 Overall Quality-of-life Score for Patients &gt;=11 to 18 Years</measure>
    <time_frame>Baseline, Week 18</time_frame>
    <description>Comparison of quality of life (from 3 age specific questionnaires) in the everolimus low-trough treatment arm (3-7 ng/mL), hightrough treatment arm (9-15 ng/mL) and placebo arm at the end of the core phase. The Quality of Life in Epilepsy Inventory for Adolescents-48 (QOLIE-AD-48) is a survey of health-related quality of life for adolescents 11 to 18 years of age with epilepsy. The QOLIE-AD-48 is completed by the patient. It contains 48 items which assess 8 subscales. Scores range from 0-100, with higher scores corresponding to improved QoL. The overall quality of life score is obtained by summing a linear combination of the 8 subscale scores, where each subscale is multiplied by a relative weight that is provided in the original publication.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Core Phase: Change From Baseline in the QOLIE-31-P Overall Quality-of-life Score for Patients Aged &gt;=18 Years</measure>
    <time_frame>Baseline, Week 18</time_frame>
    <description>Comparison of quality of life (from 3 age specific questionnaires) in the everolimus low-trough treatment arm (3-7 ng/mL), hightrough treatment arm (9-15 ng/mL) and placebo arm at the end of the core phase. The Quality of Life in Epilepsy Inventory-31-Problems (QOLIE-31-P) is a survey of health-related quality of life for adults with epilepsy. The QOLIE-31-P is completed by the patient. It contains 39 items, of which a total of 30 are used to make up 7 different subscales. Scores range from 0-100, with higher scores indicating a greater level of functioning and QoL. The overall quality of life score is obtained by summing a linear combination of the 7 subscale scores, where each subscale is multiplied by a relative weight that is obtained from the patient's answer to 7 items of this questionnaire.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Core Phase: Change From Baseline in the Overall Vineland-II Adaptive Behavior Composite (ABC) Score</measure>
    <time_frame>Baseline, 18 weeks</time_frame>
    <description>Comparison of adaptive functioning using the VABS-II composite score in the everolimus low-trough treatment arm (3-7 ng/mL), high-trough treatment arm (9-15 ng/mL) and placebo arm. The Vineland II assesses an individual's development of personal independence &amp; social responsibility. The questionnaire contains 433 items which assess 15 subdomains organized into the five domains of Communication, Daily Living Skills, Socialization, Motor Skills and Maladaptive Behavior. The overall Adaptive Behavior Composite (ABC) score is obtained by summing the standard scores of the first four domain scores for patients aged less than 7 years, or the first 3 domain scores for patients aged 7 or older (the Maladaptive Behavior domain is optional). The ABC standard score ranges from 20 to 160 with a mean of 100 and a standard deviation of 15. Higher scores correspond to improved adaptive level. Note that 2 questionnaires with ABC scores&lt;20 (data issues) were included in this analysis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Long Term Evaluation: Effect of Everolimus Over Time in the Overall Vineland-II Adaptive Behavior Composite (ABC) Score</measure>
    <time_frame>Baseline, Weeks 18, 42, 66 and 90</time_frame>
    <description>Comparison of adaptive functioning using the VABS-II composite score in the everolimus low-trough treatment arm (3-7 ng/mL), high-trough treatment arm (9-15 ng/mL) and placebo arm. The Vineland II assesses an individual's development of personal independence &amp; social responsibility. The questionnaire contains 433 items which assess 15 subdomains organized into the five domains of Communication, Daily Living Skills, Socialization, Motor Skills and Maladaptive Behavior. The overall Adaptive Behavior Composite (ABC) score is obtained by summing the standard scores of the first four domain scores for patients aged less than 7 years, or the first 3 domain scores for patients aged 7 or older (the Maladaptive Behavior domain is optional). The ABC standard score ranges from 20 to 160 with a mean of 100 and a standard deviation of 15. Higher scores correspond to improved adaptive level. Note that 2 questionnaires with ABC scores&lt;20 (data issues) were included in this analysis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Core Phase: Change From Baseline in Wechsler Nonverbal Composite Score</measure>
    <time_frame>Baseline, Week 18</time_frame>
    <description>The brief version of the WNV consists of a 2-subtest battery: only Matrices and Recognition subtests for patients under 8, and Matrices and Spatial Span subtests for patients aged 8 to 21. Based on the raw scores obtained from the subtests, standardized z-scores were calculated for each subtest using the following formula: Zscore = (X - b)/Sb where X is the raw score of the subtest, b and Sb represent the mean and standard deviation respectively of the subtest score recorded at baseline for the study population. The composite WNV score was computed by summing up the Z-scores of the 3 subtests of the WNV (i.e. matrices, recognition, and coding for patients aged &lt;8 years and matrices, spatial span, and coding for patients aged 8 to 21 years). The composite WNV score has no range.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Long Term Evaluation: Effect of Everolimus Over Time in the Overall Wechsler Nonverbal Composite Score</measure>
    <time_frame>Baseline, Weeks 18, 42, 66 and 90</time_frame>
    <description>The brief version of the WNV consists of a 2-subtest battery: only Matrices and Recognition subtests for patients under 8, and Matrices and Spatial Span subtests for patients aged 8 to 21. Based on the raw scores obtained from the subtests, standardized z-scores were calculated for each subtest using the following formula: Zscore = (X - b)/Sb where X is the raw score of the subtest, b and Sb represent the mean and standard deviation respectively of the subtest score recorded at baseline for the study population. The composite WNV score was computed by summing up the Z-scores of the 3 subtests of the WNV (i.e. matrices, recognition, and coding for patients aged &lt;8 years and matrices, spatial span, and coding for patients aged 8 to 21 years). The composite WNV score has no range</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Core Phase: Response Rate in Seizure Frequency by Time Normalized Minimum Concentration</measure>
    <time_frame>Baseline (8-week period before randomization), Week 7 to 18 (12-week maintenance period of the core phase)</time_frame>
    <description>Comparison of response rate in seizure frequency for 5 categories of time-normalized minimum concentration (Cmin, TN) (&lt; 3 ng/mL; 3-7 ng/mL; &gt;7-&lt;9 ng/mL; 9-15 ng/mL; &gt;15 ng/mL). Response rate is the percentage of patients with ≥ 50% reduction from baseline in average weekly partial-onset seizure frequency during the maintenance period of the Core phase.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Core Phase: Median Percentage Change From Baseline in Seizure Frequency by Time Normalized Minimum Concentration</measure>
    <time_frame>Baseline (8-week period before randomization), Week 7 to 18 (12-week maintenance period of the core phase)</time_frame>
    <description>Percentage change from baseline in average weekly seizure frequency during the maintenance period of the Core phase is calculated as follow: (SFcfb) = 100 × (SFB - SFM) ÷ SFB where SFB is the average weekly seizure frequency in the Baseline phase and SFM is the average weekly seizure frequency in the maintenance period of the Core phase. A positive percentage change from baseline (SFcfb) means a reduction in seizure frequency whereas a negative percentage change from baseline (SFcfb) means an increase in seizure frequency.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Long Term Evaluation: Relationship Between Seizure Frequency and Time-normalized Everolimus Concentration at Trough (Cmin,TN) - Repeated Measures Analysis</measure>
    <time_frame>During everolimus treatment from start of everolimus up to the end of the extension phase, an average of 1.7 year</time_frame>
    <description>A repeated measures analysis considering fixed 2-week intervals and including the level of exposure (time-normalized Cmin values), the time on-treatment and the seizure frequency at baseline quantified the estimated percentage change over 2 weeks in seizure frequency associated with a double exposure to everolimus, 15 days more on treatment and half the seizure frequency at baseline. A positive percentage change means a reduction in seizure frequency whereas a negative percentage change means an increase in seizure frequency.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Core Phase: Impact of Everolimus on Anti-epileptic Drugs (AEDs) Concentrations</measure>
    <time_frame>Baseline, Weeks 1 &amp; 3</time_frame>
    <description>Impact of everolimus on AED concentrations at trough. Pre-dose plasma samples to measure AED concentrations were measured at at Visits 1 (Screening), 2 (Baseline), 3, and 5. Effects of everolimus on the exposure of antiepileptic drugs was assessed by comparing the anti-epileptic drug concentrations at Visits 1 and 2 (AEDs alone) and at Visits 3 and 5 (AEDs plus everolimus).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Long Term Evaluation: Percentage Change From Start of Everolimus in Seizure Frequency by Time Window</measure>
    <time_frame>Baseline (8-week period before start of everolimus), Week 7 to 18, Week 19 to 30, and 12 weeks thereafter up to Week 102</time_frame>
    <description>Percentage change from start of everolimus in average weekly seizure frequency (SFcfe) = 100 × (SFe - SFtw) ÷ SFe where:&#xD;
SFe is the average weekly seizure frequency in the 8-week period before start of everolimus SFtw is the average weekly seizure frequency in a 12-week time window A positive percentage change from start of everolimus (SFcfe) means a reduction in seizure frequency whereas a negative percentage change from start of everolimus (SFcfe) means an increase in seizure frequency.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Seizure Free Rates by Time Window</measure>
    <time_frame>Weeks 18, 30, 42, 54, 66, 78, 90 &amp; 102</time_frame>
    <description>Percentage of seizure-free participants for each 12-week time window.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Core Phase: Incidence of Suicide Attempt, Suicidal Ideation or Behavior During Core Phase Per Columbia Suicide Severity Rating Scale (C-SSRS) Outcomes</measure>
    <time_frame>Baseline, Week 18</time_frame>
    <description>Comparison of suicidality using the C-SSRS in the everolimus low-trough treatment arm (3-7 ng/mL), high-trough treatment arm (9-15 ng/mL) and placebo arm. The Columbia-Suicide Severity Rating Scale (C-SSRS) is a questionnaire used for suicide assessment developed by multiple institutions, including Columbia University, with NIMH support. The scale is evidence-supported and is part of a national and international public health initiative involving the assessment of suicidality. There are different scoring systems depending on the population. The important elements to note are that the higher the scores on the individual items and the more &quot;yes&quot; items, the higher the suicide risk.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Long Term Evaluation: Incidence of Suicide Attempt, Suicidal Ideation or Behavior During Core Phase Per Columbia Suicide Severity Rating Scale (C-SSRS) Outcomes</measure>
    <time_frame>During everolimus treatment from start of everolimus up to permanent discontinuation of everolimus, an average of 2.3 years</time_frame>
    <description>The C-SSRS was completed at each visit. The table below presents the number of patients who reported at least one completed suicide, one suicide attempt, one preparatory action toward imminent suicidal behavior, one suicidal ideation and one self-injurious behavior without suicidal intent at any time point after starting everolimus.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">366</enrollment>
  <condition>Tuberous Sclerosis Complex-associated Refractory Seizures</condition>
  <arm_group>
    <arm_group_label>Everolimus LT target of 3 - 7 ng/mL</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received everolimus dispersible tablets for oral suspension with titration to a low trough (LT) range of 3 to 7 ng/mL plus 1 to 3 antiepileptic drugs.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Everolimus HT target of 9 -15 ng/mL</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received everolimus dispersible tablets for oral suspension with titration to a high trough (HT) range of 9 to 15 ng/mL plus 1 to 3 antiepileptic drugs.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants received placebo plus 1 to 3 antiepileptic drugs.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>RAD001</intervention_name>
    <description>Everolimus tablets for oral suspension (dispersible tablets) were packaged as 2 mg tablets in blister packs and placed in boxes with color-coded labels, color 1 or color 2.</description>
    <arm_group_label>Everolimus HT target of 9 -15 ng/mL</arm_group_label>
    <arm_group_label>Everolimus LT target of 3 - 7 ng/mL</arm_group_label>
    <other_name>everolimus</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo tablets for oral suspension (dispersible tablets) were packaged as 2 mg tablets in blister packs and placed in boxes with color-coded labels, color 1 or color 2.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Antiepileptic drug (1 to 3 only)</intervention_name>
    <description>no more than any 3 of the listed antiepileptic drugs could be taken with the study drug or placebo. List of allowed antiepileptic drugs were: valporic acid, carbamazepine, clobazam, N-desmethylclobazam, topiramate,TRI477, TRI476, clonazepam, zonisamide, phenobarbital, phenytoin</description>
    <arm_group_label>Everolimus HT target of 9 -15 ng/mL</arm_group_label>
    <arm_group_label>Everolimus LT target of 3 - 7 ng/mL</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>open label RAD001 (only used for post-extension phase)</intervention_name>
    <description>everolimus tablets for oral suspension (dispersible tablets) were packaged as 2 mg tablets in blister backs in boxes with open label design and were taken during the Post-Extension phase, where all the participants, including those who were previously on placebo, took the 2mg tablets.</description>
    <arm_group_label>Everolimus HT target of 9 -15 ng/mL</arm_group_label>
    <arm_group_label>Everolimus LT target of 3 - 7 ng/mL</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>open label everolimus</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  1. Male or female between the ages of 2 and 65 years (except in Europe where minimum&#xD;
             age will be 1).&#xD;
&#xD;
             2. Clinically definite diagnosis of TSC per modified Gomez criteria 3. Diagnosis of&#xD;
             partial-onset epilepsy according to the classification of the International League&#xD;
             Against Epilepsy (1989) and revised in 2009.&#xD;
&#xD;
             4. Uncontrolled partial-onset seizures; must meet the following:&#xD;
&#xD;
               1. At least 16 reported quantifiable partial-onset seizures over the Baseline period&#xD;
                  with no continuous 21-day seizure-free period between Visit 1 (Screening Visit)&#xD;
                  and Visit 2 (Randomization visit), as per data captured in daily seizure diaries.&#xD;
&#xD;
               2. Prior history of failure to control partial-onset seizures despite having been&#xD;
                  treated with two or more sequential regimens of single or combined antiepileptic&#xD;
                  drugs.&#xD;
&#xD;
               3. Prior or concurrent use of vagal nerve stimulator (VNS) is allowed. If the&#xD;
                  patient is using VNS, device stimulator parameters must remain constant&#xD;
                  throughout the study.&#xD;
&#xD;
               4. Prior epilepsy surgery is allowed if performed at least 12 months before study&#xD;
                  entry.&#xD;
&#xD;
                  5. Must be receiving one, two, or three AEDs at a stable dose for at least 4&#xD;
                  weeks at the start of the 8-week prospective Baseline phase, remain on the same&#xD;
                  regimen throughout the Baseline phase, and intend to continue the same regimen&#xD;
                  throughout the 18-week double blind Core phase (rescue medications are&#xD;
                  permitted).&#xD;
&#xD;
                  6. If female of child bearing potential, documentation of negative pregnancy test&#xD;
                  at time of informed consent and must use highly effective contraception during&#xD;
                  the study and for 8 weeks after stopping treatment 7. Sexually active males must&#xD;
                  use a condom during intercourse while taking study drug, and for 8 weeks after&#xD;
                  stopping study treatment 8. Hepatic, renal and blood laboratory values within the&#xD;
                  following range at screening :&#xD;
&#xD;
               1. AST and ALT levels &lt; 2.5 x ULN&#xD;
&#xD;
               2. serum bilirubin &lt;1.5 × ULN (this limit does not apply to patients with an&#xD;
                  elevated indirect bilirubin, if they have Gilbert's Syndrome),&#xD;
&#xD;
               3. serum creatinine &lt; 1.5 x ULN&#xD;
&#xD;
               4. hemoglobin ≥ 9 g/dL&#xD;
&#xD;
               5. platelets ≥ 80,000/mm3&#xD;
&#xD;
               6. absolute neutrophil count ≥ 1,000/mm3 9. Written informed consent. Subjects or&#xD;
                  their legal guardians must have the ability to comprehend the informed consent&#xD;
                  form and be willing to provide informed consent.&#xD;
&#xD;
                  10. Patient or caregiver must be able to reliably record seizures and keep a&#xD;
                  daily diary and recall adverse events.&#xD;
&#xD;
                  Exclusion Criteria:&#xD;
&#xD;
          -  1. Patients with seizures secondary to metabolic, toxic, infectious or psychogenic&#xD;
             disorder or drug abuse or current seizures related to an acute medical illness.&#xD;
&#xD;
             2. Presence of only non-motor partial seizures (NOT APPLICABLE per Amendment 2) 3.&#xD;
             Patients with TSC who have SEGA in need of immediate surgical intervention. 4.&#xD;
             Patients under 2 years of age with untreated infantile spasms. 5. Within 52 weeks&#xD;
             prior to study entry, an episode of status epilepticus as defined in the protocol.&#xD;
&#xD;
             6. Patients with history of seizure clusters (where individual seizures cannot be&#xD;
             accurately counted according to the judgment of the investigator) occurring within 26&#xD;
             weeks prior to study entry.&#xD;
&#xD;
             7. Patients who require rescue medication during the baseline phase for more than 6&#xD;
             days 8. Patients with non-TSC related progressive encephalopathy. 9. Patients who&#xD;
             weigh less than 12 kg. 10. Patients with coexisting malignancies within the 3 years&#xD;
             prior to randomization, except for adequately treated carcinoma of the cervix or basal&#xD;
             or squamous cell carcinomas of the skin.&#xD;
&#xD;
             11. Patients with any severe and/or uncontrolled medical conditions at randomization&#xD;
             such as:&#xD;
&#xD;
               1. Symptomatic congestive heart failure of New York Heart Association Class III or&#xD;
                  IV, history of left ventricular ejection fraction (LVEF) &lt; 50%, QTc interval&#xD;
                  &gt;460ms, congenital QT syndrome, unstable angina pectoris, myocardial infarction&#xD;
                  within 6 months of study entry, serious uncontrolled cardiac arrhythmia or any&#xD;
                  other clinically significant cardiac disease.&#xD;
&#xD;
               2. Significant symptomatic deterioration of lung function&#xD;
&#xD;
               3. Impairment of gastrointestinal function or gastrointestinal disease that may&#xD;
                  significantly alter the absorption of everolimus (e.g., ulcerative disease,&#xD;
                  malabsorption syndrome or small bowel resection).&#xD;
&#xD;
               4. liver disease such as cirrhosis, decompensated liver disease, and chronic&#xD;
                  hepatitis&#xD;
&#xD;
               5. Uncontrolled diabetes as defined by fasting serum glucose &gt; 1.5 × ULN.&#xD;
&#xD;
               6. Active skin, mucosa, ocular or GI disorders of Grade &gt; 1.&#xD;
&#xD;
               7. Active (acute or chronic) or uncontrolled severe infections.&#xD;
&#xD;
               8. A known history of HIV seropositivity or other active viral infections. 12.&#xD;
                  Patients with an active, bleeding diathesis. 13. Patient with uncontrolled&#xD;
                  hyperlipidemia: fasting serum cholesterol &gt; 300 mg/dL OR &gt;7.75 mmol/L AND fasting&#xD;
                  triglycerides &gt; 2.5 x ULN.&#xD;
&#xD;
                  14. Patients who have had a major surgery or significant traumatic injury within&#xD;
                  4 weeks of study entry.&#xD;
&#xD;
                  15. Patients with a prior history of organ transplant. 16. Patients receiving&#xD;
                  more than 3 antiepileptic drugs at any time in the baseline phase or at&#xD;
                  randomization or who change the dose of the AEDs during 4 weeks before screening&#xD;
                  or during the baseline period.&#xD;
&#xD;
                  17. Patients being treated with felbamate, unless treatment has been continuous&#xD;
                  for ≥ 1 year.&#xD;
&#xD;
                  18. Patients currently receiving anticancer therapies or who have received&#xD;
                  anticancer therapies within 4 weeks of study entry (including chemotherapy,&#xD;
                  radiation therapy, antibody based therapy, etc.).&#xD;
&#xD;
                  19. Prior treatment with any investigational drug within the preceding 4 weeks&#xD;
                  prior to study entry.&#xD;
&#xD;
                  20. Patients receiving chronic, systemic treatment with corticosteroids or&#xD;
                  another immunosuppressive agent at study entry. Topical or inhaled&#xD;
                  corticosteroids are allowed.&#xD;
&#xD;
                  21. Patients who have received prior treatment with a systemic mTOR inhibitor&#xD;
                  (sirolimus, temsirolimus, everolimus) within 24 months of study entry. Patients&#xD;
                  who have received prior treatment with a topical mTOR inhibitor (sirolimus,&#xD;
                  temsirolimus, everolimus) within 4 weeks of study entry.&#xD;
&#xD;
                  22. Patients with a known hypersensitivity to everolimus or other&#xD;
                  rapamycin-analogues (sirolimus, temsirolimus) or to its excipients.&#xD;
&#xD;
                  23. Patients with a history of non-compliance to medical regimens or who are&#xD;
                  considered potentially unreliable or will not be able to complete the entire&#xD;
                  study 24. Pregnant or nursing (lactating) women, where pregnancy is defined as&#xD;
                  the state of a female after conception and until the termination of gestation,&#xD;
                  confirmed by a positive hCG laboratory test.&#xD;
&#xD;
                  25. Patients with a Score of 4 or 5 on the Suicidal Ideation item within 2 years&#xD;
                  of Screening, or any &quot;yes&quot; on the Suicidal Behavior item of the Columbia-Suicide&#xD;
                  Severity Rating Scale at Screening or Baseline , who upon follow up with a&#xD;
                  healthcare professional are found to be severely depressed or suicidal.&#xD;
&#xD;
                  26. Maintenance of a diet consisting of &lt;40 g of carbohydrate per day within 3&#xD;
                  months of screening&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>2 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Novartis Pharmaceuticals</last_name>
    <role>Study Director</role>
    <affiliation>Novartis Pharmaceuticals</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Alabama at Birmingham SC</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35294</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>TGen/APNNA</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85012</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California at Los Angeles SC</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90095</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital Oakland SC</name>
      <address>
        <city>Oakland</city>
        <state>California</state>
        <zip>94609</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital of Orange County SC</name>
      <address>
        <city>Orange</city>
        <state>California</state>
        <zip>92868-3874</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rady Children's Hospital SC</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92123</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>Connecticut Childrens Medical Center SC</name>
      <address>
        <city>Hartford</city>
        <state>Connecticut</state>
        <zip>06106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Chicago SC - 2</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60637</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kennedy Krieger Institute SC</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital Boston SC</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Minnesota Epilepsy Group - PA SC</name>
      <address>
        <city>Saint Paul</city>
        <state>Minnesota</state>
        <zip>55102-2383</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington University School of Medicine SC-2</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Morristown Memorial Hospital SC-2</name>
      <address>
        <city>Morristown</city>
        <state>New Jersey</state>
        <zip>07962</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>New York University Medical Center SC-3</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cincinnati Children's Hospital Medical Center SC</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45229-3039</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oregon Health and Science University SC - 3</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 SC</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104-4399</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>LeBonheur Childrens Medical Group SC</name>
      <address>
        <city>Memphis</city>
        <state>Tennessee</state>
        <zip>38103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Scottish Rite Hospital for Children Texas Scottish</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75219</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Children s Hospital SC</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The University of Texas Medical School-Houston SC</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Caba</city>
        <state>Buenos Aires</state>
        <zip>C1428AQK</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Cordoba</city>
        <zip>X5000JJS</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Randwick</city>
        <state>New South Wales</state>
        <zip>2031</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Parkville</city>
        <state>Victoria</state>
        <zip>3052</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Perth</city>
        <state>Western Australia</state>
        <zip>6840</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Jette</city>
        <state>Brussel</state>
        <zip>1090</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Bruxelles</city>
        <zip>1070</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Bruxelles</city>
        <zip>1200</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Gent</city>
        <zip>9000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Leuven</city>
        <zip>3000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Vancouver</city>
        <state>British Columbia</state>
        <zip>V6H 3V4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H3T 1C5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Cali</city>
        <state>Valle Del Cauca</state>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Bogotá</city>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Medellín</city>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Aarhus</city>
        <zip>8000 C</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Amiens Cedex 1</city>
        <zip>80054</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Angers cedex 09</city>
        <zip>49933</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Bron Cedex</city>
        <zip>69677</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Lille Cedex</city>
        <zip>59037</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Marseille</city>
        <zip>13385</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Strasbourg Cedex</city>
        <zip>F-67098</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Berlin</city>
        <zip>12351</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Bielefeld</city>
        <zip>33617</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Kehl-Kork</city>
        <zip>77694</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Kiel</city>
        <zip>24105</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Ioannina</city>
        <state>GR</state>
        <zip>455 00</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Athens</city>
        <zip>15236</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Budapest</city>
        <zip>1145</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Kaposvar</city>
        <zip>7400</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Nyiregyhaza</city>
        <zip>4400</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Dublin</city>
        <zip>12</zip>
        <country>Ireland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Bari</city>
        <state>BA</state>
        <zip>70124</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Bologna</city>
        <state>BO</state>
        <zip>40133</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Catania</city>
        <state>CT</state>
        <zip>95100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Genova</city>
        <state>GE</state>
        <zip>16147</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Milano</city>
        <state>MI</state>
        <zip>20142</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Pavia</city>
        <state>PV</state>
        <zip>27100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Roma</city>
        <state>RM</state>
        <zip>00161</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Siena</city>
        <state>SI</state>
        <zip>53100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Okayama-city</city>
        <state>Okayama</state>
        <zip>700-8558</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Izumi-city</city>
        <state>Osaka</state>
        <zip>594-1101</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Suita-city</city>
        <state>Osaka</state>
        <zip>565 0871</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Shizuoka-city</city>
        <state>Shizuoka</state>
        <zip>420-8688</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Setagaya-ku</city>
        <state>Tokyo</state>
        <zip>157-8535</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Osaka</city>
        <zip>534-0021</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Seoul</city>
        <state>Korea</state>
        <zip>03080</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Seoul</city>
        <state>Korea</state>
        <zip>05505</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Seoul</city>
        <state>Korea</state>
        <zip>06351</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Seoul</city>
        <zip>03722</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Guadalajara</city>
        <state>Jalisco</state>
        <zip>44280</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Heeze</city>
        <zip>5591 VE</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Rotterdam</city>
        <zip>3015 CN</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Utrecht</city>
        <zip>3584CX</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Oslo</city>
        <zip>0424</zip>
        <country>Norway</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Warszawa</city>
        <zip>04 730</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Samara</city>
        <state>Samara Region</state>
        <zip>443095</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Voronezh</city>
        <state>Voronezh Region</state>
        <zip>394024</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Moscow</city>
        <zip>119991</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Moscow</city>
        <zip>127412</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Sevilla</city>
        <state>Andalucía</state>
        <zip>41013</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Barcelona</city>
        <state>Catalunya</state>
        <zip>08035</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Valencia</city>
        <state>Comunidad Valenciana</state>
        <zip>46026</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>San Sebastian</city>
        <state>Pais Vasco</state>
        <zip>20080</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Madrid</city>
        <zip>28009</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Tainan</city>
        <state>Taiwan ROC</state>
        <zip>70421</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Kaohsiung City</city>
        <zip>83301</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Taipei</city>
        <zip>10002</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Bangkok</city>
        <zip>10330</zip>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Bangkok</city>
        <zip>10400</zip>
        <country>Thailand</country>
      </address>
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  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Bangkok</city>
        <zip>10700</zip>
        <country>Thailand</country>
      </address>
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  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Ankara</city>
        <zip>06100</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Ankara</city>
        <zip>06500</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Istanbul</city>
        <zip>34093</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Birmingham</city>
        <zip>B15 2WB</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Buckinghamshire</city>
        <zip>SL9 0RJ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Cambridge</city>
        <zip>CB2 2QQ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Liverpool</city>
        <zip>L12 2AP</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>London</city>
        <zip>SW17 0QT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>London</city>
        <zip>WC1N 3JH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Sheffield</city>
        <zip>S10 2TH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>York</city>
        <zip>YO31 7EX</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Argentina</country>
    <country>Australia</country>
    <country>Belgium</country>
    <country>Canada</country>
    <country>Colombia</country>
    <country>Denmark</country>
    <country>France</country>
    <country>Germany</country>
    <country>Greece</country>
    <country>Hungary</country>
    <country>Ireland</country>
    <country>Italy</country>
    <country>Japan</country>
    <country>Korea, Republic of</country>
    <country>Mexico</country>
    <country>Netherlands</country>
    <country>Norway</country>
    <country>Poland</country>
    <country>Russian Federation</country>
    <country>Spain</country>
    <country>Taiwan</country>
    <country>Thailand</country>
    <country>Turkey</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Sweden</country>
  </removed_countries>
  <verification_date>November 2018</verification_date>
  <study_first_submitted>October 9, 2012</study_first_submitted>
  <study_first_submitted_qc>October 22, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 25, 2012</study_first_posted>
  <results_first_submitted>April 25, 2018</results_first_submitted>
  <results_first_submitted_qc>November 6, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">November 7, 2018</results_first_posted>
  <last_update_submitted>November 6, 2018</last_update_submitted>
  <last_update_submitted_qc>November 6, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">November 7, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>TSC seizures</keyword>
  <keyword>TSC epilepsy</keyword>
  <keyword>mTOR inhibitor</keyword>
  <keyword>RAD001</keyword>
  <keyword>Everolimus</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tuberous Sclerosis</mesh_term>
    <mesh_term>Seizures</mesh_term>
    <mesh_term>Sclerosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Everolimus</mesh_term>
    <mesh_term>Anticonvulsants</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.&#xD;
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com</ipd_description>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>March 25, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/46/NCT01713946/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 11, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/46/NCT01713946/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>355 patients were planned to be enrolled and a total of 366 patients were randomized: 117 to the everolimus targeted low-trough arm (LT), 130 to the everolimus targeted high-trough (HT) arm, and 119 to treatment with placebo.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Everolimus LT Target of 3 to 7 ng/mL</title>
          <description>Participants were randomized to receive everolimus dispersible tablets for oral suspension with titration to a low trough (LT) range of 3 to 7 ng/mL</description>
        </group>
        <group group_id="P2">
          <title>Everolimus HT Target of 9 to 15 ng/mL</title>
          <description>Participants were randomized to receive everolimus dispersible tablets for oral suspension with titration to a high trough (HT) range of 9 to 15 ng/mL</description>
        </group>
        <group group_id="P3">
          <title>Placebo</title>
          <description>Participants who received placebo dispersible tablets for oral suspension at study start and switched to everolimus in Extension.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="117"/>
                <participants group_id="P2" count="130"/>
                <participants group_id="P3" count="119">Of the 119 patients initially randomized to the Placebo arm, 5 patients never switched to everolimus</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>Completed Core Phase</title>
              <participants_list>
                <participants group_id="P1" count="110"/>
                <participants group_id="P2" count="122"/>
                <participants group_id="P3" count="114"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Continued in Ext. Phase</title>
              <participants_list>
                <participants group_id="P1" count="110"/>
                <participants group_id="P2" count="119"/>
                <participants group_id="P3" count="114"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Completed Ext. Phase</title>
              <participants_list>
                <participants group_id="P1" count="79"/>
                <participants group_id="P2" count="92"/>
                <participants group_id="P3" count="81"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Continued in Post-Ext. Phase</title>
              <participants_list>
                <participants group_id="P1" count="78"/>
                <participants group_id="P2" count="90"/>
                <participants group_id="P3" count="81"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Completed Post-Ext Phase</title>
              <participants_list>
                <participants group_id="P1" count="74"/>
                <participants group_id="P2" count="85"/>
                <participants group_id="P3" count="75"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Did Not Continue in Ext Phase</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Did Not Cont. in Post-Ext Phase</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="74"/>
                <participants group_id="P2" count="85"/>
                <participants group_id="P3" count="75"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="43"/>
                <participants group_id="P2" count="45"/>
                <participants group_id="P3" count="44"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="19"/>
                <participants group_id="P2" count="14"/>
                <participants group_id="P3" count="13"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="12"/>
                <participants group_id="P3" count="8"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="8"/>
                <participants group_id="P3" count="14"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="4"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Administrative problems</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Did not continue in Ext</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Did not continue in Post-Ext. Phase</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Patients never switched to everolimus</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="5"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Full Analysis Set: The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization.</population>
      <group_list>
        <group group_id="B1">
          <title>Everolimus LT Target of 3 to 7 ng/mL</title>
          <description>Participants were randomized to receive everolimus dispersible tablets for oral suspension with titration to a low trough (LT) range of 3 to 7 ng/mL</description>
        </group>
        <group group_id="B2">
          <title>Everolimus HT Target of 9 to 15 ng/mL</title>
          <description>Participants were randomized to receive everolimus dispersible tablets for oral suspension with titration to a high trough (HT) range of 9 to 15 ng/mL</description>
        </group>
        <group group_id="B3">
          <title>Placebo</title>
          <description>Participants were randomized to receive placebo dispersible tablets for oral suspension.</description>
        </group>
        <group group_id="B4">
          <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="117"/>
            <count group_id="B2" value="130"/>
            <count group_id="B3" value="119"/>
            <count group_id="B4" value="366"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <population>The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization.</population>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9.72" lower_limit="2.2" upper_limit="56.3"/>
                    <measurement group_id="B2" value="10.08" lower_limit="2.3" upper_limit="50.5"/>
                    <measurement group_id="B3" value="10.34" lower_limit="2.2" upper_limit="52.0"/>
                    <measurement group_id="B4" value="10.06" lower_limit="2.2" upper_limit="56.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age, Customized</title>
          <population>The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>&lt; 6 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="33"/>
                    <measurement group_id="B2" value="37"/>
                    <measurement group_id="B3" value="34"/>
                    <measurement group_id="B4" value="104"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>6 to &lt;12 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="37"/>
                    <measurement group_id="B2" value="39"/>
                    <measurement group_id="B3" value="37"/>
                    <measurement group_id="B4" value="113"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>12 to &lt;18 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="26"/>
                    <measurement group_id="B2" value="31"/>
                    <measurement group_id="B3" value="25"/>
                    <measurement group_id="B4" value="82"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>18 to &lt;65 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="21"/>
                    <measurement group_id="B2" value="23"/>
                    <measurement group_id="B3" value="23"/>
                    <measurement group_id="B4" value="67"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <population>The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="53"/>
                    <measurement group_id="B2" value="65"/>
                    <measurement group_id="B3" value="58"/>
                    <measurement group_id="B4" value="176"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="64"/>
                    <measurement group_id="B2" value="65"/>
                    <measurement group_id="B3" value="61"/>
                    <measurement group_id="B4" value="190"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <population>The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Caucasian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="76"/>
                    <measurement group_id="B2" value="84"/>
                    <measurement group_id="B3" value="77"/>
                    <measurement group_id="B4" value="237"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Asian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="29"/>
                    <measurement group_id="B2" value="31"/>
                    <measurement group_id="B3" value="27"/>
                    <measurement group_id="B4" value="87"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Black</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Native American</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pacific Islander</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Other</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="14"/>
                    <measurement group_id="B4" value="36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Weight</title>
          <population>The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization.</population>
          <units>kg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="38.69" spread="22.802"/>
                    <measurement group_id="B2" value="40.75" spread="27.267"/>
                    <measurement group_id="B3" value="40.50" spread="24.923"/>
                    <measurement group_id="B4" value="40.01" spread="25.093"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Height</title>
          <population>The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization.</population>
          <units>cm</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="135.65" spread="26.171"/>
                    <measurement group_id="B2" value="136.25" spread="28.234"/>
                    <measurement group_id="B3" value="135.67" spread="27.097"/>
                    <measurement group_id="B4" value="135.87" spread="27.145"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Body surface area</title>
          <population>The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization.</population>
          <units>m^2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1.18" spread="0.437"/>
                    <measurement group_id="B2" value="1.20" spread="0.501"/>
                    <measurement group_id="B3" value="1.20" spread="0.476"/>
                    <measurement group_id="B4" value="1.20" spread="0.472"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Body mass index</title>
          <population>The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization.</population>
          <units>kg/m^2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="19.29" spread="5.283"/>
                    <measurement group_id="B2" value="19.56" spread="6.233"/>
                    <measurement group_id="B3" value="19.78" spread="5.484"/>
                    <measurement group_id="B4" value="19.55" spread="5.689"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Core Phase: European Medicine Agency (EMA): Seizure Frequency Response Rate</title>
        <description>Comparison of response rates in the everolimus low-trough treatment arm (3-7 ng/mL), high-trough treatment arm (9-15 ng/mL) and placebo arm. Response means at least a 50% reduction from baseline in partial-onset seizure frequency during the maintenance period of the core phase.</description>
        <time_frame>Baseline (8-week period before randomization), Week 7 to 18 (12-week maintenance period of the core phase)</time_frame>
        <population>The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization</population>
        <group_list>
          <group group_id="O1">
            <title>Everolimus LT Target of 3 to 7 ng/mL</title>
            <description>Participants were randomized to receive everolimus dispersible tablets for oral suspension with titration to a low trough (LT) range of 3 to 7 ng/mL</description>
          </group>
          <group group_id="O2">
            <title>Everolimus HT Target of 9 to 15 ng/mL</title>
            <description>Participants were randomized to receive everolimus dispersible tablets for oral suspension with titration to a high trough (HT) range of 9 to 15 ng/mL</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>Participants were randomized to receive placebo dispersible tablets for oral suspension.</description>
          </group>
        </group_list>
        <measure>
          <title>Core Phase: European Medicine Agency (EMA): Seizure Frequency Response Rate</title>
          <description>Comparison of response rates in the everolimus low-trough treatment arm (3-7 ng/mL), high-trough treatment arm (9-15 ng/mL) and placebo arm. Response means at least a 50% reduction from baseline in partial-onset seizure frequency during the maintenance period of the core phase.</description>
          <population>The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization</population>
          <units>Percentage of responders</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="117"/>
                <count group_id="O2" value="130"/>
                <count group_id="O3" value="119"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="28.2" lower_limit="20.3" upper_limit="37.3"/>
                    <measurement group_id="O2" value="40.0" lower_limit="31.5" upper_limit="49.0"/>
                    <measurement group_id="O3" value="15.1" lower_limit="9.2" upper_limit="22.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.008</p_value>
            <method>Bonferroni-Holm</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>2.21</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.16</ci_lower_limit>
            <ci_upper_limit>4.20</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>Bonferroni-Holm</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>3.93</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>2.10</ci_lower_limit>
            <ci_upper_limit>7.32</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Core Phase: Food &amp; Drug Administration (FDA): Percentage Change From Baseline in Partial Onset-seizure Frequency</title>
        <description>Comparison of median percent change from baseline in weekly seizure frequency in the everolimus low-trough treatment arm (3-7 ng/mL), high-trough treatment arm (9-15 ng/mL) and placebo arm during maintenance period of the core phase. Percentage change from baseline in average weekly seizure frequency during the maintenance period of the Core phase (SFcfb) = 100 × (SFB - SFM) ÷ SFB where:&#xD;
SFB is the average weekly seizure frequency in the Baseline phase SFM is the average weekly seizure frequency in the maintenance period of the Core phase A positive percentage change from baseline (SFcfb) means a reduction in seizure frequency whereas a negative percentage change from baseline (SFcfb) means an increase in seizure frequency.</description>
        <time_frame>Baseline (8-week period before randomization), Week 7 to 18 (12-week maintenance period of the core phase)</time_frame>
        <population>The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization</population>
        <group_list>
          <group group_id="O1">
            <title>Everolimus LT Target of 3 to 7 ng/mL</title>
            <description>Participants were randomized to receive everolimus dispersible tablets for oral suspension with titration to a low trough (LT) range of 3 to 7 ng/mL</description>
          </group>
          <group group_id="O2">
            <title>Everolimus HT Target of 9 to 15 ng/mL</title>
            <description>Participants were randomized to receive everolimus dispersible tablets for oral suspension with titration to a high trough (HT) range of 9 to 15 ng/mL</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>Participants were randomized to receive placebo dispersible tablets for oral suspension.</description>
          </group>
        </group_list>
        <measure>
          <title>Core Phase: Food &amp; Drug Administration (FDA): Percentage Change From Baseline in Partial Onset-seizure Frequency</title>
          <description>Comparison of median percent change from baseline in weekly seizure frequency in the everolimus low-trough treatment arm (3-7 ng/mL), high-trough treatment arm (9-15 ng/mL) and placebo arm during maintenance period of the core phase. Percentage change from baseline in average weekly seizure frequency during the maintenance period of the Core phase (SFcfb) = 100 × (SFB - SFM) ÷ SFB where:&#xD;
SFB is the average weekly seizure frequency in the Baseline phase SFM is the average weekly seizure frequency in the maintenance period of the Core phase A positive percentage change from baseline (SFcfb) means a reduction in seizure frequency whereas a negative percentage change from baseline (SFcfb) means an increase in seizure frequency.</description>
          <population>The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization</population>
          <units>Percentage change from baseline</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="117"/>
                <count group_id="O2" value="130"/>
                <count group_id="O3" value="119"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29.29" lower_limit="18.82" upper_limit="41.88"/>
                    <measurement group_id="O2" value="39.55" lower_limit="35.03" upper_limit="48.74"/>
                    <measurement group_id="O3" value="14.86" lower_limit="0.11" upper_limit="21.71"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.003</p_value>
            <method>Bonferroni-Holm</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>15.96</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.98</ci_lower_limit>
            <ci_upper_limit>31.68</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>Bonferroni-Holm</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>27.46</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>16.36</ci_lower_limit>
            <ci_upper_limit>43.36</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Seizure-free Patients During the Maintenance Period of the Core Phase</title>
        <description>Comparison of seizure freedom (100% reduction in seizure frequency) in the everolimus low-trough treatment arm (3-7 ng/mL), high-trough treatment arm (9-15 ng/mL) and placebo arm during maintenance period of the core phase. Seizure free means a 100% reduction from baseline in partial-onset seizure frequency during maintenance period of the core phase.</description>
        <time_frame>Baseline (8-week period before randomization), Week 7 to 18 (12-week maintenance period of the core phase)</time_frame>
        <population>The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization</population>
        <group_list>
          <group group_id="O1">
            <title>Everolimus LT Target of 3 to 7 ng/mL</title>
            <description>Participants were randomized to receive everolimus dispersible tablets for oral suspension with titration to a low trough (LT) range of 3 to 7 ng/mL</description>
          </group>
          <group group_id="O2">
            <title>Everolimus HT Target of 9 to 15 ng/mL</title>
            <description>Participants were randomized to receive everolimus dispersible tablets for oral suspension with titration to a high trough (HT) range of 9 to 15 ng/mL</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>Participants were randomized to receive placebo dispersible tablets for oral suspension.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Seizure-free Patients During the Maintenance Period of the Core Phase</title>
          <description>Comparison of seizure freedom (100% reduction in seizure frequency) in the everolimus low-trough treatment arm (3-7 ng/mL), high-trough treatment arm (9-15 ng/mL) and placebo arm during maintenance period of the core phase. Seizure free means a 100% reduction from baseline in partial-onset seizure frequency during maintenance period of the core phase.</description>
          <population>The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization</population>
          <units>Percentage of seizure-free 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="117"/>
                <count group_id="O2" value="130"/>
                <count group_id="O3" value="119"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.1" lower_limit="1.9" upper_limit="10.8"/>
                    <measurement group_id="O2" value="3.8" lower_limit="1.3" upper_limit="8.7"/>
                    <measurement group_id="O3" value="0.8" lower_limit="0.0" upper_limit="4.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>6.55</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.77</ci_lower_limit>
            <ci_upper_limit>55.73</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>4.99</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.57</ci_lower_limit>
            <ci_upper_limit>44.03</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Core Phase: Percentage of Patients With at Least a 25% Reduction in Seizure Frequency</title>
        <description>Comparison of percentage of patients with at least ≥ 25% reduction in seizure frequency in the everolimus low-trough treatment arm (3-7 ng/mL), high-trough treatment arm (9-15 ng/mL) and placebo arm during maintenance period of the core phase. At least 25% reduction from baseline in partial-onset seizure frequency during maintenance period of the core phase.</description>
        <time_frame>Baseline (8-week period before randomization), Week 7 to 18 (12-week maintenance period of the core phase)</time_frame>
        <population>The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization</population>
        <group_list>
          <group group_id="O1">
            <title>Everolimus LT Target of 3 to 7 ng/mL</title>
            <description>Participants were randomized to receive everolimus dispersible tablets for oral suspension with titration to a low trough (LT) range of 3 to 7 ng/mL</description>
          </group>
          <group group_id="O2">
            <title>Everolimus HT Target of 9 to 15 ng/mL</title>
            <description>Participants were randomized to receive everolimus dispersible tablets for oral suspension with titration to a high trough (HT) range of 9 to 15 ng/mL</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>Participants were randomized to receive placebo dispersible tablets for oral suspension.</description>
          </group>
        </group_list>
        <measure>
          <title>Core Phase: Percentage of Patients With at Least a 25% Reduction in Seizure Frequency</title>
          <description>Comparison of percentage of patients with at least ≥ 25% reduction in seizure frequency in the everolimus low-trough treatment arm (3-7 ng/mL), high-trough treatment arm (9-15 ng/mL) and placebo arm during maintenance period of the core phase. At least 25% reduction from baseline in partial-onset seizure frequency during maintenance period of the core phase.</description>
          <population>The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization</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="117"/>
                <count group_id="O2" value="130"/>
                <count group_id="O3" value="119"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="52.1" lower_limit="42.7" upper_limit="61.5"/>
                    <measurement group_id="O2" value="70.0" lower_limit="61.3" upper_limit="77.7"/>
                    <measurement group_id="O3" value="37.8" lower_limit="29.1" upper_limit="47.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>1.77</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.05</ci_lower_limit>
            <ci_upper_limit>2.97</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>3.82</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>2.25</ci_lower_limit>
            <ci_upper_limit>6.48</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Core Phase: Distribution of Reduction From Baseline in Seizure Frequency</title>
        <description>Comparison of percentage of patients in six categories of seizure reduction from baseline (≤ -25% (exacerbation); &gt; -25% to &lt; 25% (no change); ≥ 25% to &lt; 50%; ≥ 50% to &lt; 75%; ≥ 75% to &lt; 100%; 100% (seizure-freedom)) in the everolimus low-trough treatment arm (3-7 ng/mL), high-trough treatment arm (9-15 ng/mL) and placebo arm during maintenance period of the core phase</description>
        <time_frame>Baseline (8-week period before randomization), Week 7 to 18 (12-week maintenance period of the core phase)</time_frame>
        <population>The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization</population>
        <group_list>
          <group group_id="O1">
            <title>Everolimus LT Target of 3 to 7 ng/mL</title>
            <description>Participants were randomized to receive everolimus dispersible tablets for oral suspension with titration to a low trough (LT) range of 3 to 7 ng/mL</description>
          </group>
          <group group_id="O2">
            <title>Everolimus HT Target of 9 to 15 ng/mL</title>
            <description>Participants were randomized to receive everolimus dispersible tablets for oral suspension with titration to a high trough (HT) range of 9 to 15 ng/mL</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>Participants were randomized to receive placebo dispersible tablets for oral suspension.</description>
          </group>
        </group_list>
        <measure>
          <title>Core Phase: Distribution of Reduction From Baseline in Seizure Frequency</title>
          <description>Comparison of percentage of patients in six categories of seizure reduction from baseline (≤ -25% (exacerbation); &gt; -25% to &lt; 25% (no change); ≥ 25% to &lt; 50%; ≥ 50% to &lt; 75%; ≥ 75% to &lt; 100%; 100% (seizure-freedom)) in the everolimus low-trough treatment arm (3-7 ng/mL), high-trough treatment arm (9-15 ng/mL) and placebo arm during maintenance period of the core phase</description>
          <population>The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="117"/>
                <count group_id="O2" value="130"/>
                <count group_id="O3" value="119"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>100% (seizure free)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.1"/>
                    <measurement group_id="O2" value="3.8"/>
                    <measurement group_id="O3" value="0.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>≥ 75 to &lt;100 (75% responder)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.0"/>
                    <measurement group_id="O2" value="15.4"/>
                    <measurement group_id="O3" value="5.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>≥ 50 to &lt;75 (50% responder)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17.1"/>
                    <measurement group_id="O2" value="20.8"/>
                    <measurement group_id="O3" value="9.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>≥ 25 to &lt;50 (25% responder)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23.9"/>
                    <measurement group_id="O2" value="30.0"/>
                    <measurement group_id="O3" value="22.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&gt;-25 to &lt;25 (No change)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="35.0"/>
                    <measurement group_id="O2" value="18.5"/>
                    <measurement group_id="O3" value="41.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>≤ -25 (Exacerbation)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.8"/>
                    <measurement group_id="O2" value="11.5"/>
                    <measurement group_id="O3" value="20.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Missing (missing)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0"/>
                    <measurement group_id="O2" value="0.0"/>
                    <measurement group_id="O3" value="0.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Core Phase: Changes From Baseline in Number of Seizure-free Days</title>
        <description>Comparison of seizure-free days relative to baseline in the everolimus low-trough treatment arm (3-7 ng/mL), high-trough treatment arm (9-15 ng/mL) and placebo arm during maintenance period of the core phase</description>
        <time_frame>Baseline (8-week period before randomization), Week 7 to 18 (12-week maintenance period of the core phase)</time_frame>
        <population>The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization</population>
        <group_list>
          <group group_id="O1">
            <title>Everolimus LT Target of 3 to 7 ng/mL</title>
            <description>Participants were randomized to receive everolimus dispersible tablets for oral suspension with titration to a low trough (LT) range of 3 to 7 ng/mL</description>
          </group>
          <group group_id="O2">
            <title>Everolimus HT Target of 9 to 15 ng/mL</title>
            <description>Participants were randomized to receive everolimus dispersible tablets for oral suspension with titration to a high trough (HT) range of 9 to 15 ng/mL</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>Participants were randomized to receive placebo dispersible tablets for oral suspension.</description>
          </group>
        </group_list>
        <measure>
          <title>Core Phase: Changes From Baseline in Number of Seizure-free Days</title>
          <description>Comparison of seizure-free days relative to baseline in the everolimus low-trough treatment arm (3-7 ng/mL), high-trough treatment arm (9-15 ng/mL) and placebo arm during maintenance period of the core phase</description>
          <population>The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization</population>
          <units>Number of seizure-free days -per 28 days</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="117"/>
                <count group_id="O2" value="130"/>
                <count group_id="O3" value="119"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.00" lower_limit="-23.1" upper_limit="27.7"/>
                    <measurement group_id="O2" value="4.01" lower_limit="-10.0" upper_limit="27.5"/>
                    <measurement group_id="O3" value="0.47" lower_limit="-13.4" upper_limit="21.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>1.4</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.4</ci_lower_limit>
            <ci_upper_limit>3.1</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>4.2</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>2.5</ci_lower_limit>
            <ci_upper_limit>5.9</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Core Phase: Probability That a Patient Remains On-treatment up to a Specified Time Point</title>
        <description>Comparison of time to treatment discontinuation in the everolimus low-trough treatment arm (3-7 ng/mL), high-trough treatment arm (9-15 ng/mL) and placebo arm during the core phase. Treatment duration is defined as the time from randomization until the date of permanent study treatment discontinuation (for any reason) at any time during the Core phase.&#xD;
The percentage event-free probability estimate is the estimated probability that a patient will remain on-treatment up to a specified time point (Week 6, 12, 18)</description>
        <time_frame>Week 6, Week 12, Week 18</time_frame>
        <population>The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization</population>
        <group_list>
          <group group_id="O1">
            <title>Everolimus LT Target of 3 to 7 ng/mL</title>
            <description>Participants were randomized to receive everolimus dispersible tablets for oral suspension with titration to a low trough (LT) range of 3 to 7 ng/mL</description>
          </group>
          <group group_id="O2">
            <title>Everolimus HT Target of 9 to 15 ng/mL</title>
            <description>Participants were randomized to receive everolimus dispersible tablets for oral suspension with titration to a high trough (HT) range of 9 to 15 ng/mL</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>Participants were randomized to receive placebo dispersible tablets for oral suspension.</description>
          </group>
        </group_list>
        <measure>
          <title>Core Phase: Probability That a Patient Remains On-treatment up to a Specified Time Point</title>
          <description>Comparison of time to treatment discontinuation in the everolimus low-trough treatment arm (3-7 ng/mL), high-trough treatment arm (9-15 ng/mL) and placebo arm during the core phase. Treatment duration is defined as the time from randomization until the date of permanent study treatment discontinuation (for any reason) at any time during the Core phase.&#xD;
The percentage event-free probability estimate is the estimated probability that a patient will remain on-treatment up to a specified time point (Week 6, 12, 18)</description>
          <population>The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization</population>
          <units>Percentage event-free prob. estimates</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="117"/>
                <count group_id="O2" value="130"/>
                <count group_id="O3" value="119"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="97.4" lower_limit="92.3" upper_limit="99.2"/>
                    <measurement group_id="O2" value="96.2" lower_limit="91.0" upper_limit="98.4"/>
                    <measurement group_id="O3" value="99.2" lower_limit="94.2" upper_limit="99.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="95.7" lower_limit="90.0" upper_limit="98.2"/>
                    <measurement group_id="O2" value="95.4" lower_limit="90.0" upper_limit="97.9"/>
                    <measurement group_id="O3" value="97.5" lower_limit="92.4" upper_limit="99.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 18</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="70.1" lower_limit="60.9" upper_limit="77.5"/>
                    <measurement group_id="O2" value="71.5" lower_limit="62.9" upper_limit="78.5"/>
                    <measurement group_id="O3" value="75.6" lower_limit="66.9" upper_limit="82.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>1.27</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.77</ci_lower_limit>
            <ci_upper_limit>2.07</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>1.20</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.74</ci_lower_limit>
            <ci_upper_limit>1.96</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Core Phase: Change From Baseline in the QOLCE Overall Quality-of-life Score for Patients &lt;11 Years</title>
        <description>Comparison of quality of life in the everolimus (from 3 age specific questionnaires) low-trough treatment arm (3-7 ng/mL), high-trough treatment arm (9-15 ng/mL) and placebo arm at the end of the core phase. The Quality of Life Childhood Epilepsy (QOLCE) questionnaire, used for patients &lt; 11 years at baseline, was completed by the patient's parent or caregiver. It consists of 16 subscales (13 multi-item scales and 3 single item scales) and one overall quality-of-life score. Scores range from 0-100, with higher scores corresponding to improved QoL. The Overall Quality of Life Score is computed by adding each subscale score for each individual and then dividing by 16.</description>
        <time_frame>Baseline, Week 18</time_frame>
        <population>The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization</population>
        <group_list>
          <group group_id="O1">
            <title>Everolimus LT Target of 3 to 7 ng/mL</title>
            <description>Participants were randomized to receive everolimus dispersible tablets for oral suspension with titration to a low trough (LT) range of 3 to 7 ng/mL</description>
          </group>
          <group group_id="O2">
            <title>Everolimus HT Target of 9 to 15 ng/mL</title>
            <description>Participants were randomized to receive everolimus dispersible tablets for oral suspension with titration to a high trough (HT) range of 9 to 15 ng/mL</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>Participants were randomized to receive placebo dispersible tablets for oral suspension.</description>
          </group>
        </group_list>
        <measure>
          <title>Core Phase: Change From Baseline in the QOLCE Overall Quality-of-life Score for Patients &lt;11 Years</title>
          <description>Comparison of quality of life in the everolimus (from 3 age specific questionnaires) low-trough treatment arm (3-7 ng/mL), high-trough treatment arm (9-15 ng/mL) and placebo arm at the end of the core phase. The Quality of Life Childhood Epilepsy (QOLCE) questionnaire, used for patients &lt; 11 years at baseline, was completed by the patient's parent or caregiver. It consists of 16 subscales (13 multi-item scales and 3 single item scales) and one overall quality-of-life score. Scores range from 0-100, with higher scores corresponding to improved QoL. The Overall Quality of Life Score is computed by adding each subscale score for each individual and then dividing by 16.</description>
          <population>The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization</population>
          <units>scores on a scale</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="65"/>
                <count group_id="O2" value="69"/>
                <count group_id="O3" value="63"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="63"/>
                    <count group_id="O2" value="68"/>
                    <count group_id="O3" value="55"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="52.3" lower_limit="26" upper_limit="75"/>
                    <measurement group_id="O2" value="56.5" lower_limit="26" upper_limit="76"/>
                    <measurement group_id="O3" value="55.3" lower_limit="33" upper_limit="74"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>End of Core Phase</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="56"/>
                    <count group_id="O2" value="56"/>
                    <count group_id="O3" value="50"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="53.6" lower_limit="24" upper_limit="79"/>
                    <measurement group_id="O2" value="59.5" lower_limit="36" upper_limit="78"/>
                    <measurement group_id="O3" value="57.2" lower_limit="20" upper_limit="77"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="55"/>
                    <count group_id="O2" value="56"/>
                    <count group_id="O3" value="47"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.2" lower_limit="-25" upper_limit="24"/>
                    <measurement group_id="O2" value="0.0" lower_limit="-19" upper_limit="18"/>
                    <measurement group_id="O3" value="1.0" lower_limit="-18" upper_limit="28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <param_type>Difference in least square means</param_type>
            <param_value>-1.1</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-4.4</ci_lower_limit>
            <ci_upper_limit>2.1</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <param_type>Difference in least square means</param_type>
            <param_value>1.0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-2.2</ci_lower_limit>
            <ci_upper_limit>4.3</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Core Phase: Change From Baseline in the QOLIE-AD-48 Overall Quality-of-life Score for Patients &gt;=11 to 18 Years</title>
        <description>Comparison of quality of life (from 3 age specific questionnaires) in the everolimus low-trough treatment arm (3-7 ng/mL), hightrough treatment arm (9-15 ng/mL) and placebo arm at the end of the core phase. The Quality of Life in Epilepsy Inventory for Adolescents-48 (QOLIE-AD-48) is a survey of health-related quality of life for adolescents 11 to 18 years of age with epilepsy. The QOLIE-AD-48 is completed by the patient. It contains 48 items which assess 8 subscales. Scores range from 0-100, with higher scores corresponding to improved QoL. The overall quality of life score is obtained by summing a linear combination of the 8 subscale scores, where each subscale is multiplied by a relative weight that is provided in the original publication.</description>
        <time_frame>Baseline, Week 18</time_frame>
        <population>The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization</population>
        <group_list>
          <group group_id="O1">
            <title>Everolimus LT Target of 3 to 7 ng/mL</title>
            <description>Participants were randomized to receive everolimus dispersible tablets for oral suspension with titration to a low trough (LT) range of 3 to 7 ng/mL</description>
          </group>
          <group group_id="O2">
            <title>Everolimus HT Target of 9 to 15 ng/mL</title>
            <description>Participants were randomized to receive everolimus dispersible tablets for oral suspension with titration to a high trough (HT) range of 9 to 15 ng/mL</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>Participants were randomized to receive placebo dispersible tablets for oral suspension.</description>
          </group>
        </group_list>
        <measure>
          <title>Core Phase: Change From Baseline in the QOLIE-AD-48 Overall Quality-of-life Score for Patients &gt;=11 to 18 Years</title>
          <description>Comparison of quality of life (from 3 age specific questionnaires) in the everolimus low-trough treatment arm (3-7 ng/mL), hightrough treatment arm (9-15 ng/mL) and placebo arm at the end of the core phase. The Quality of Life in Epilepsy Inventory for Adolescents-48 (QOLIE-AD-48) is a survey of health-related quality of life for adolescents 11 to 18 years of age with epilepsy. The QOLIE-AD-48 is completed by the patient. It contains 48 items which assess 8 subscales. Scores range from 0-100, with higher scores corresponding to improved QoL. The overall quality of life score is obtained by summing a linear combination of the 8 subscale scores, where each subscale is multiplied by a relative weight that is provided in the original publication.</description>
          <population>The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization</population>
          <units>scores on a scale</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="31"/>
                <count group_id="O2" value="38"/>
                <count group_id="O3" value="33"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="13"/>
                    <count group_id="O2" value="15"/>
                    <count group_id="O3" value="14"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="56.1" lower_limit="43" upper_limit="86"/>
                    <measurement group_id="O2" value="58.8" lower_limit="35" upper_limit="81"/>
                    <measurement group_id="O3" value="59.6" lower_limit="13" upper_limit="88"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>End of Core Phase</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="13"/>
                    <count group_id="O2" value="13"/>
                    <count group_id="O3" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="58.5" lower_limit="47" upper_limit="89"/>
                    <measurement group_id="O2" value="60.7" lower_limit="46" upper_limit="74"/>
                    <measurement group_id="O3" value="65.4" lower_limit="29" upper_limit="87"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="12"/>
                    <count group_id="O2" value="13"/>
                    <count group_id="O3" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.7" lower_limit="-11" upper_limit="11"/>
                    <measurement group_id="O2" value="5.8" lower_limit="-13" upper_limit="38"/>
                    <measurement group_id="O3" value="7.2" lower_limit="-18" upper_limit="25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <param_type>Difference in least square means</param_type>
            <param_value>-2.1</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-10.5</ci_lower_limit>
            <ci_upper_limit>6.2</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <param_type>Difference in least square means</param_type>
            <param_value>0.4</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-7.8</ci_lower_limit>
            <ci_upper_limit>8.6</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Core Phase: Change From Baseline in the QOLIE-31-P Overall Quality-of-life Score for Patients Aged &gt;=18 Years</title>
        <description>Comparison of quality of life (from 3 age specific questionnaires) in the everolimus low-trough treatment arm (3-7 ng/mL), hightrough treatment arm (9-15 ng/mL) and placebo arm at the end of the core phase. The Quality of Life in Epilepsy Inventory-31-Problems (QOLIE-31-P) is a survey of health-related quality of life for adults with epilepsy. The QOLIE-31-P is completed by the patient. It contains 39 items, of which a total of 30 are used to make up 7 different subscales. Scores range from 0-100, with higher scores indicating a greater level of functioning and QoL. The overall quality of life score is obtained by summing a linear combination of the 7 subscale scores, where each subscale is multiplied by a relative weight that is obtained from the patient's answer to 7 items of this questionnaire.</description>
        <time_frame>Baseline, Week 18</time_frame>
        <population>The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization</population>
        <group_list>
          <group group_id="O1">
            <title>Everolimus LT Target of 3 to 7 ng/mL</title>
            <description>Participants were randomized to receive everolimus dispersible tablets for oral suspension with titration to a low trough (LT) range of 3 to 7 ng/mL</description>
          </group>
          <group group_id="O2">
            <title>Everolimus HT Target of 9 to 15 ng/mL</title>
            <description>Participants were randomized to receive everolimus dispersible tablets for oral suspension with titration to a high trough (HT) range of 9 to 15 ng/mL</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>Participants were randomized to receive placebo dispersible tablets for oral suspension.</description>
          </group>
        </group_list>
        <measure>
          <title>Core Phase: Change From Baseline in the QOLIE-31-P Overall Quality-of-life Score for Patients Aged &gt;=18 Years</title>
          <description>Comparison of quality of life (from 3 age specific questionnaires) in the everolimus low-trough treatment arm (3-7 ng/mL), hightrough treatment arm (9-15 ng/mL) and placebo arm at the end of the core phase. The Quality of Life in Epilepsy Inventory-31-Problems (QOLIE-31-P) is a survey of health-related quality of life for adults with epilepsy. The QOLIE-31-P is completed by the patient. It contains 39 items, of which a total of 30 are used to make up 7 different subscales. Scores range from 0-100, with higher scores indicating a greater level of functioning and QoL. The overall quality of life score is obtained by summing a linear combination of the 7 subscale scores, where each subscale is multiplied by a relative weight that is obtained from the patient's answer to 7 items of this questionnaire.</description>
          <population>The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization</population>
          <units>scores on a scale</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
                <count group_id="O2" value="23"/>
                <count group_id="O3" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="11"/>
                    <count group_id="O2" value="11"/>
                    <count group_id="O3" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="39.5" lower_limit="13" upper_limit="64"/>
                    <measurement group_id="O2" value="43.2" lower_limit="5" upper_limit="89"/>
                    <measurement group_id="O3" value="43.6" lower_limit="11" upper_limit="83"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>End of Core Phase</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                    <count group_id="O2" value="11"/>
                    <count group_id="O3" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="48.6" lower_limit="11" upper_limit="54"/>
                    <measurement group_id="O2" value="37.1" lower_limit="6" upper_limit="97"/>
                    <measurement group_id="O3" value="54.8" lower_limit="26" upper_limit="90"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                    <count group_id="O2" value="11"/>
                    <count group_id="O3" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.5" lower_limit="-17" upper_limit="34"/>
                    <measurement group_id="O2" value="0.4" lower_limit="-47" upper_limit="20"/>
                    <measurement group_id="O3" value="5.3" lower_limit="-16" upper_limit="36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <param_type>Difference in least square means</param_type>
            <param_value>-2.8</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-17.9</ci_lower_limit>
            <ci_upper_limit>12.3</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <param_type>Difference in least square means</param_type>
            <param_value>-7.7</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-22.0</ci_lower_limit>
            <ci_upper_limit>6.6</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Core Phase: Change From Baseline in the Overall Vineland-II Adaptive Behavior Composite (ABC) Score</title>
        <description>Comparison of adaptive functioning using the VABS-II composite score in the everolimus low-trough treatment arm (3-7 ng/mL), high-trough treatment arm (9-15 ng/mL) and placebo arm. The Vineland II assesses an individual's development of personal independence &amp; social responsibility. The questionnaire contains 433 items which assess 15 subdomains organized into the five domains of Communication, Daily Living Skills, Socialization, Motor Skills and Maladaptive Behavior. The overall Adaptive Behavior Composite (ABC) score is obtained by summing the standard scores of the first four domain scores for patients aged less than 7 years, or the first 3 domain scores for patients aged 7 or older (the Maladaptive Behavior domain is optional). The ABC standard score ranges from 20 to 160 with a mean of 100 and a standard deviation of 15. Higher scores correspond to improved adaptive level. Note that 2 questionnaires with ABC scores&lt;20 (data issues) were included in this analysis.</description>
        <time_frame>Baseline, 18 weeks</time_frame>
        <population>The safety Set comprised all patients who received at least one dose of study treatment and had at least one post-baseline safety assessment in the Core phase (where the statement that a patient had no AE constitutes a safety assessment).</population>
        <group_list>
          <group group_id="O1">
            <title>Everolimus LT Target of 3 to 7 ng/mL</title>
            <description>Participants were randomized to receive everolimus dispersible tablets for oral suspension with titration to a low trough (LT) range of 3 to 7 ng/mL</description>
          </group>
          <group group_id="O2">
            <title>Everolimus HT Target of 9 to 15 ng/mL</title>
            <description>Participants were randomized to receive everolimus dispersible tablets for oral suspension with titration to a high trough (HT) range of 9 to 15 ng/mL</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>Participants were randomized to receive placebo dispersible tablets for oral suspension.</description>
          </group>
        </group_list>
        <measure>
          <title>Core Phase: Change From Baseline in the Overall Vineland-II Adaptive Behavior Composite (ABC) Score</title>
          <description>Comparison of adaptive functioning using the VABS-II composite score in the everolimus low-trough treatment arm (3-7 ng/mL), high-trough treatment arm (9-15 ng/mL) and placebo arm. The Vineland II assesses an individual's development of personal independence &amp; social responsibility. The questionnaire contains 433 items which assess 15 subdomains organized into the five domains of Communication, Daily Living Skills, Socialization, Motor Skills and Maladaptive Behavior. The overall Adaptive Behavior Composite (ABC) score is obtained by summing the standard scores of the first four domain scores for patients aged less than 7 years, or the first 3 domain scores for patients aged 7 or older (the Maladaptive Behavior domain is optional). The ABC standard score ranges from 20 to 160 with a mean of 100 and a standard deviation of 15. Higher scores correspond to improved adaptive level. Note that 2 questionnaires with ABC scores&lt;20 (data issues) were included in this analysis.</description>
          <population>The safety Set comprised all patients who received at least one dose of study treatment and had at least one post-baseline safety assessment in the Core phase (where the statement that a patient had no AE constitutes a safety assessment).</population>
          <units>scores on a scale</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="75"/>
                <count group_id="O2" value="93"/>
                <count group_id="O3" value="76"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="34"/>
                    <count group_id="O2" value="34"/>
                    <count group_id="O3" value="32"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="58.00" lower_limit="20.0" upper_limit="112.0"/>
                    <measurement group_id="O2" value="56.50" lower_limit="20.0" upper_limit="102.0"/>
                    <measurement group_id="O3" value="55.00" lower_limit="20.0" upper_limit="103.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>End of Core Phase</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="28"/>
                    <count group_id="O2" value="39"/>
                    <count group_id="O3" value="31"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="54.00" lower_limit="6.0" upper_limit="121.0"/>
                    <measurement group_id="O2" value="55.00" lower_limit="20.0" upper_limit="111.0"/>
                    <measurement group_id="O3" value="55.00" lower_limit="20.0" upper_limit="105.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                    <count group_id="O2" value="23"/>
                    <count group_id="O3" value="23"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.00" lower_limit="-21.0" upper_limit="15.0"/>
                    <measurement group_id="O2" value="0.00" lower_limit="-13.0" upper_limit="15.0"/>
                    <measurement group_id="O3" value="0.00" lower_limit="-12.0" upper_limit="10.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Long Term Evaluation: Effect of Everolimus Over Time in the Overall Vineland-II Adaptive Behavior Composite (ABC) Score</title>
        <description>Comparison of adaptive functioning using the VABS-II composite score in the everolimus low-trough treatment arm (3-7 ng/mL), high-trough treatment arm (9-15 ng/mL) and placebo arm. The Vineland II assesses an individual's development of personal independence &amp; social responsibility. The questionnaire contains 433 items which assess 15 subdomains organized into the five domains of Communication, Daily Living Skills, Socialization, Motor Skills and Maladaptive Behavior. The overall Adaptive Behavior Composite (ABC) score is obtained by summing the standard scores of the first four domain scores for patients aged less than 7 years, or the first 3 domain scores for patients aged 7 or older (the Maladaptive Behavior domain is optional). The ABC standard score ranges from 20 to 160 with a mean of 100 and a standard deviation of 15. Higher scores correspond to improved adaptive level. Note that 2 questionnaires with ABC scores&lt;20 (data issues) were included in this analysis.</description>
        <time_frame>Baseline, Weeks 18, 42, 66 and 90</time_frame>
        <population>The Long Term Evaluation (LTE) efficacy set consists of all patients who received at least one dose of everolimus and had at least one efficacy assessment while on everolimus.</population>
        <group_list>
          <group group_id="O1">
            <title>Everolimus LT Target of 3 to 7 ng/mL</title>
            <description>Participants were randomized to receive everolimus dispersible tablets for oral suspension with titration to a low trough (LT) range of 3 to 7 ng/mL</description>
          </group>
          <group group_id="O2">
            <title>Everolimus HT Target of 9 to 15 ng/mL</title>
            <description>Participants were randomized to receive everolimus dispersible tablets for oral suspension with titration to a high trough (HT) range of 9 to 15 ng/mL</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>Participants were randomized to receive placebo dispersible tablets for oral suspension.</description>
          </group>
          <group group_id="O4">
            <title>Everolimus Long Term Evaluation (LTE)</title>
            <description>Participants who were treated with everolimus either in the Core or Extension phases of the study and were evaluated for longer term safety and efficacy.</description>
          </group>
        </group_list>
        <measure>
          <title>Long Term Evaluation: Effect of Everolimus Over Time in the Overall Vineland-II Adaptive Behavior Composite (ABC) Score</title>
          <description>Comparison of adaptive functioning using the VABS-II composite score in the everolimus low-trough treatment arm (3-7 ng/mL), high-trough treatment arm (9-15 ng/mL) and placebo arm. The Vineland II assesses an individual's development of personal independence &amp; social responsibility. The questionnaire contains 433 items which assess 15 subdomains organized into the five domains of Communication, Daily Living Skills, Socialization, Motor Skills and Maladaptive Behavior. The overall Adaptive Behavior Composite (ABC) score is obtained by summing the standard scores of the first four domain scores for patients aged less than 7 years, or the first 3 domain scores for patients aged 7 or older (the Maladaptive Behavior domain is optional). The ABC standard score ranges from 20 to 160 with a mean of 100 and a standard deviation of 15. Higher scores correspond to improved adaptive level. Note that 2 questionnaires with ABC scores&lt;20 (data issues) were included in this analysis.</description>
          <population>The Long Term Evaluation (LTE) efficacy set consists of all patients who received at least one dose of everolimus and had at least one efficacy assessment while on everolimus.</population>
          <units>scores on a scale</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
                <count group_id="O3" value="0"/>
                <count group_id="O4" value="239"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="0"/>
                    <count group_id="O4" value="88"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O4" value="56.00" lower_limit="20.0" upper_limit="112.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 18</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="0"/>
                    <count group_id="O4" value="94"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O4" value="53.50" lower_limit="4.0" upper_limit="121.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 42</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="0"/>
                    <count group_id="O4" value="94"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O4" value="55.50" lower_limit="20.0" upper_limit="111.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 66</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="0"/>
                    <count group_id="O4" value="88"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O4" value="57.00" lower_limit="20.0" upper_limit="112.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 90</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="0"/>
                    <count group_id="O4" value="66"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O4" value="49.50" lower_limit="20.0" upper_limit="150.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Core Phase: Change From Baseline in Wechsler Nonverbal Composite Score</title>
        <description>The brief version of the WNV consists of a 2-subtest battery: only Matrices and Recognition subtests for patients under 8, and Matrices and Spatial Span subtests for patients aged 8 to 21. Based on the raw scores obtained from the subtests, standardized z-scores were calculated for each subtest using the following formula: Zscore = (X - b)/Sb where X is the raw score of the subtest, b and Sb represent the mean and standard deviation respectively of the subtest score recorded at baseline for the study population. The composite WNV score was computed by summing up the Z-scores of the 3 subtests of the WNV (i.e. matrices, recognition, and coding for patients aged &lt;8 years and matrices, spatial span, and coding for patients aged 8 to 21 years). The composite WNV score has no range.</description>
        <time_frame>Baseline, Week 18</time_frame>
        <population>The safety Set comprised all patients who received at least one dose of study treatment and had at least one post-baseline safety assessment in the Core phase (where the statement that a patient had no AE constitutes a safety assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>Everolimus LT Target of 3 to 7 ng/mL</title>
            <description>Participants were randomized to receive everolimus dispersible tablets for oral suspension with titration to a low trough (LT) range of 3 to 7 ng/mL</description>
          </group>
          <group group_id="O2">
            <title>Everolimus HT Target of 9 to 15 ng/mL</title>
            <description>Participants were randomized to receive everolimus dispersible tablets for oral suspension with titration to a high trough (HT) range of 9 to 15 ng/mL</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>Participants were randomized to receive placebo dispersible tablets for oral suspension.</description>
          </group>
          <group group_id="O4">
            <title>Everolimus Long Term Evaluation (LTE)</title>
            <description>Participants who were treated with everolimus either in the Core or Extension phases of the study and were evaluated for longer term safety and efficacy.</description>
          </group>
        </group_list>
        <measure>
          <title>Core Phase: Change From Baseline in Wechsler Nonverbal Composite Score</title>
          <description>The brief version of the WNV consists of a 2-subtest battery: only Matrices and Recognition subtests for patients under 8, and Matrices and Spatial Span subtests for patients aged 8 to 21. Based on the raw scores obtained from the subtests, standardized z-scores were calculated for each subtest using the following formula: Zscore = (X - b)/Sb where X is the raw score of the subtest, b and Sb represent the mean and standard deviation respectively of the subtest score recorded at baseline for the study population. The composite WNV score was computed by summing up the Z-scores of the 3 subtests of the WNV (i.e. matrices, recognition, and coding for patients aged &lt;8 years and matrices, spatial span, and coding for patients aged 8 to 21 years). The composite WNV score has no range.</description>
          <population>The safety Set comprised all patients who received at least one dose of study treatment and had at least one post-baseline safety assessment in the Core phase (where the statement that a patient had no AE constitutes a safety assessment.</population>
          <units>scores on a scale</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="89"/>
                <count group_id="O2" value="94"/>
                <count group_id="O3" value="85"/>
                <count group_id="O4" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="63"/>
                    <count group_id="O2" value="63"/>
                    <count group_id="O3" value="52"/>
                    <count group_id="O4" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.48" lower_limit="-2.3" upper_limit="8.1"/>
                    <measurement group_id="O2" value="-0.69" lower_limit="-2.3" upper_limit="9.6"/>
                    <measurement group_id="O3" value="-1.11" lower_limit="-2.3" upper_limit="8.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>End of Core Phase</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="60"/>
                    <count group_id="O2" value="63"/>
                    <count group_id="O3" value="48"/>
                    <count group_id="O4" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.04" lower_limit="-2.3" upper_limit="8.1"/>
                    <measurement group_id="O2" value="-0.89" lower_limit="-2.3" upper_limit="7.5"/>
                    <measurement group_id="O3" value="-0.51" lower_limit="-2.3" upper_limit="10.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="58"/>
                    <count group_id="O2" value="59"/>
                    <count group_id="O3" value="46"/>
                    <count group_id="O4" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.00" lower_limit="-2.5" upper_limit="1.6"/>
                    <measurement group_id="O2" value="0.00" lower_limit="-10.0" upper_limit="2.1"/>
                    <measurement group_id="O3" value="0.00" lower_limit="-3.3" upper_limit="1.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Long Term Evaluation: Effect of Everolimus Over Time in the Overall Wechsler Nonverbal Composite Score</title>
        <description>The brief version of the WNV consists of a 2-subtest battery: only Matrices and Recognition subtests for patients under 8, and Matrices and Spatial Span subtests for patients aged 8 to 21. Based on the raw scores obtained from the subtests, standardized z-scores were calculated for each subtest using the following formula: Zscore = (X - b)/Sb where X is the raw score of the subtest, b and Sb represent the mean and standard deviation respectively of the subtest score recorded at baseline for the study population. The composite WNV score was computed by summing up the Z-scores of the 3 subtests of the WNV (i.e. matrices, recognition, and coding for patients aged &lt;8 years and matrices, spatial span, and coding for patients aged 8 to 21 years). The composite WNV score has no range</description>
        <time_frame>Baseline, Weeks 18, 42, 66 and 90</time_frame>
        <population>The Long Term Evaluation (LTE) efficacy set consists of all patients who received at least one dose of everolimus and had at least one efficacy assessment while on everolimus.</population>
        <group_list>
          <group group_id="O1">
            <title>Everolimus LT Target of 3 to 7 ng/mL</title>
            <description>Participants were randomized to receive everolimus dispersible tablets for oral suspension with titration to a low trough (LT) range of 3 to 7 ng/mL</description>
          </group>
          <group group_id="O2">
            <title>Everolimus HT Target of 9 to 15 ng/mL</title>
            <description>Participants were randomized to receive everolimus dispersible tablets for oral suspension with titration to a high trough (HT) range of 9 to 15 ng/mL</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>Participants were randomized to receive placebo dispersible tablets for oral suspension.</description>
          </group>
          <group group_id="O4">
            <title>Everolimus Long Term Evaluation (LTE)</title>
            <description>Participants who were treated with everolimus either in the Core or Extension phases of the study and were evaluated for longer term safety and efficacy.</description>
          </group>
        </group_list>
        <measure>
          <title>Long Term Evaluation: Effect of Everolimus Over Time in the Overall Wechsler Nonverbal Composite Score</title>
          <description>The brief version of the WNV consists of a 2-subtest battery: only Matrices and Recognition subtests for patients under 8, and Matrices and Spatial Span subtests for patients aged 8 to 21. Based on the raw scores obtained from the subtests, standardized z-scores were calculated for each subtest using the following formula: Zscore = (X - b)/Sb where X is the raw score of the subtest, b and Sb represent the mean and standard deviation respectively of the subtest score recorded at baseline for the study population. The composite WNV score was computed by summing up the Z-scores of the 3 subtests of the WNV (i.e. matrices, recognition, and coding for patients aged &lt;8 years and matrices, spatial span, and coding for patients aged 8 to 21 years). The composite WNV score has no range</description>
          <population>The Long Term Evaluation (LTE) efficacy set consists of all patients who received at least one dose of everolimus and had at least one efficacy assessment while on everolimus.</population>
          <units>scores on a scale</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
                <count group_id="O3" value="0"/>
                <count group_id="O4" value="265"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="0"/>
                    <count group_id="O4" value="151"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O4" value="-0.53" lower_limit="-2.3" upper_limit="10.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 18</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="0"/>
                    <count group_id="O4" value="160"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O4" value="-0.44" lower_limit="-2.3" upper_limit="9.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 42</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="0"/>
                    <count group_id="O4" value="139"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O4" value="-0.36" lower_limit="-2.3" upper_limit="10.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 66</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="0"/>
                    <count group_id="O4" value="104"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O4" value="0.13" lower_limit="-2.3" upper_limit="9.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 90</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="0"/>
                    <count group_id="O4" value="82"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O4" value="-0.06" lower_limit="-2.3" upper_limit="9.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Core Phase: Response Rate in Seizure Frequency by Time Normalized Minimum Concentration</title>
        <description>Comparison of response rate in seizure frequency for 5 categories of time-normalized minimum concentration (Cmin, TN) (&lt; 3 ng/mL; 3-7 ng/mL; &gt;7-&lt;9 ng/mL; 9-15 ng/mL; &gt;15 ng/mL). Response rate is the percentage of patients with ≥ 50% reduction from baseline in average weekly partial-onset seizure frequency during the maintenance period of the Core phase.</description>
        <time_frame>Baseline (8-week period before randomization), Week 7 to 18 (12-week maintenance period of the core phase)</time_frame>
        <population>Confirmed PK Sample Set from all everolimus-treated patients in the Safety Set was defined as: Cmin collected prior to dose administration on the same treatment day and 20-28 hours after the previous dose, at steady state, and with no evidence of vomiting within 4 hours of the previous dose.</population>
        <group_list>
          <group group_id="O1">
            <title>&lt;3 ng/mL</title>
            <description>Observed TN-Cmin concentration during the maintenance of the core phase: &lt;3 ng/mL</description>
          </group>
          <group group_id="O2">
            <title>3-7 ng/mL</title>
            <description>Observed TN-Cmin concentration during the maintenance of the core phase:3 - 7 ng/mL</description>
          </group>
          <group group_id="O3">
            <title>&gt;7-&lt;9 ng/mL</title>
            <description>Observed TN-Cmin concentration during the maintenance of the core phase: &gt;7 - &lt;9 ng/mL</description>
          </group>
          <group group_id="O4">
            <title>9-15 ng/mL</title>
            <description>Observed TN-Cmin concentration during the maintenance of the core phase: 9 - 15 ng/mL</description>
          </group>
          <group group_id="O5">
            <title>&gt;15 ng/mL</title>
            <description>Observed TN-Cmin concentration during the maintenance of the core phase: &gt;15 ng/mL</description>
          </group>
        </group_list>
        <measure>
          <title>Core Phase: Response Rate in Seizure Frequency by Time Normalized Minimum Concentration</title>
          <description>Comparison of response rate in seizure frequency for 5 categories of time-normalized minimum concentration (Cmin, TN) (&lt; 3 ng/mL; 3-7 ng/mL; &gt;7-&lt;9 ng/mL; 9-15 ng/mL; &gt;15 ng/mL). Response rate is the percentage of patients with ≥ 50% reduction from baseline in average weekly partial-onset seizure frequency during the maintenance period of the Core phase.</description>
          <population>Confirmed PK Sample Set from all everolimus-treated patients in the Safety Set was defined as: Cmin collected prior to dose administration on the same treatment day and 20-28 hours after the previous dose, at steady state, and with no evidence of vomiting within 4 hours of the previous dose.</population>
          <units>Percentage of responders</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="14"/>
                <count group_id="O2" value="147"/>
                <count group_id="O3" value="52"/>
                <count group_id="O4" value="30"/>
                <count group_id="O5" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14.3" lower_limit="1.8" upper_limit="42.8"/>
                    <measurement group_id="O2" value="29.9" lower_limit="22.7" upper_limit="38.0"/>
                    <measurement group_id="O3" value="44.2" lower_limit="30.5" upper_limit="58.7"/>
                    <measurement group_id="O4" value="50.0" lower_limit="31.3" upper_limit="68.7"/>
                    <measurement group_id="O5" value="50.0" lower_limit="1.3" upper_limit="98.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Core Phase: Median Percentage Change From Baseline in Seizure Frequency by Time Normalized Minimum Concentration</title>
        <description>Percentage change from baseline in average weekly seizure frequency during the maintenance period of the Core phase is calculated as follow: (SFcfb) = 100 × (SFB - SFM) ÷ SFB where SFB is the average weekly seizure frequency in the Baseline phase and SFM is the average weekly seizure frequency in the maintenance period of the Core phase. A positive percentage change from baseline (SFcfb) means a reduction in seizure frequency whereas a negative percentage change from baseline (SFcfb) means an increase in seizure frequency.</description>
        <time_frame>Baseline (8-week period before randomization), Week 7 to 18 (12-week maintenance period of the core phase)</time_frame>
        <population>Confirmed PK Sample Set from all everolimus-treated patients in the Safety Set was defined as: Cmin collected prior to dose administration on the same treatment day and 20-28 hours after the previous dose, at steady state, and with no evidence of vomiting within 4 hours of the previous dose.</population>
        <group_list>
          <group group_id="O1">
            <title>&lt;3 ng/mL</title>
            <description>Observed TN-Cmin concentration during the maintenance of the core phase: &lt;3 ng/mL</description>
          </group>
          <group group_id="O2">
            <title>3-7 ng/mL</title>
            <description>Observed TN-Cmin concentration during the maintenance of the core phase:3 - 7 ng/mL</description>
          </group>
          <group group_id="O3">
            <title>&gt;7-&lt;9 ng/mL</title>
            <description>Observed TN-Cmin concentration during the maintenance of the core phase: &gt;7 - &lt;9 ng/mL</description>
          </group>
          <group group_id="O4">
            <title>9-15 ng/mL</title>
            <description>Observed TN-Cmin concentration during the maintenance of the core phase: 9 - 15 ng/mL</description>
          </group>
          <group group_id="O5">
            <title>&gt;15 ng/mL</title>
            <description>Observed TN-Cmin concentration during the maintenance of the core phase: &gt;15 ng/mL</description>
          </group>
        </group_list>
        <measure>
          <title>Core Phase: Median Percentage Change From Baseline in Seizure Frequency by Time Normalized Minimum Concentration</title>
          <description>Percentage change from baseline in average weekly seizure frequency during the maintenance period of the Core phase is calculated as follow: (SFcfb) = 100 × (SFB - SFM) ÷ SFB where SFB is the average weekly seizure frequency in the Baseline phase and SFM is the average weekly seizure frequency in the maintenance period of the Core phase. A positive percentage change from baseline (SFcfb) means a reduction in seizure frequency whereas a negative percentage change from baseline (SFcfb) means an increase in seizure frequency.</description>
          <population>Confirmed PK Sample Set from all everolimus-treated patients in the Safety Set was defined as: Cmin collected prior to dose administration on the same treatment day and 20-28 hours after the previous dose, at steady state, and with no evidence of vomiting within 4 hours of the previous dose.</population>
          <units>Percentage change</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="14"/>
                <count group_id="O2" value="147"/>
                <count group_id="O3" value="52"/>
                <count group_id="O4" value="30"/>
                <count group_id="O5" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20.55" lower_limit="-8.45" upper_limit="35.39"/>
                    <measurement group_id="O2" value="35.56" lower_limit="24.43" upper_limit="41.88"/>
                    <measurement group_id="O3" value="39.72" lower_limit="28.02" upper_limit="62.79"/>
                    <measurement group_id="O4" value="47.69" lower_limit="36.46" upper_limit="66.32"/>
                    <measurement group_id="O5" value="61.56" lower_limit="42.73" upper_limit="80.38"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Long Term Evaluation: Relationship Between Seizure Frequency and Time-normalized Everolimus Concentration at Trough (Cmin,TN) - Repeated Measures Analysis</title>
        <description>A repeated measures analysis considering fixed 2-week intervals and including the level of exposure (time-normalized Cmin values), the time on-treatment and the seizure frequency at baseline quantified the estimated percentage change over 2 weeks in seizure frequency associated with a double exposure to everolimus, 15 days more on treatment and half the seizure frequency at baseline. A positive percentage change means a reduction in seizure frequency whereas a negative percentage change means an increase in seizure frequency.</description>
        <time_frame>During everolimus treatment from start of everolimus up to the end of the extension phase, an average of 1.7 year</time_frame>
        <population>Confirmed PK Sample Set from all everolimus-treated patients in the Longer-term Evaluation (LTE) Safety Set, was defined as follows: Cmin collected prior to dose administration on the same treatment day and 20-28 hours after the previous dose, at steady state, and with no evidence of vomiting within 4 hours of the previous dose</population>
        <group_list>
          <group group_id="O1">
            <title>Everolimus LT Target of 3 to 7 ng/mL</title>
            <description>Participants were randomized to receive everolimus dispersible tablets for oral suspension with titration to a low trough (LT) range of 3 to 7 ng/mL</description>
          </group>
          <group group_id="O2">
            <title>Everolimus HT Target of 9 to 15 ng/mL</title>
            <description>Participants were randomized to receive everolimus dispersible tablets for oral suspension with titration to a high trough (HT) range of 9 to 15 ng/mL</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>Participants were randomized to receive placebo dispersible tablets for oral suspension.</description>
          </group>
          <group group_id="O4">
            <title>Everolimus Long Term Evaluation (LTE)</title>
            <description>Participants who were treated with everolimus either in the Core or Extension phases of the study and were evaluated for longer term safety and efficacy.</description>
          </group>
        </group_list>
        <measure>
          <title>Long Term Evaluation: Relationship Between Seizure Frequency and Time-normalized Everolimus Concentration at Trough (Cmin,TN) - Repeated Measures Analysis</title>
          <description>A repeated measures analysis considering fixed 2-week intervals and including the level of exposure (time-normalized Cmin values), the time on-treatment and the seizure frequency at baseline quantified the estimated percentage change over 2 weeks in seizure frequency associated with a double exposure to everolimus, 15 days more on treatment and half the seizure frequency at baseline. A positive percentage change means a reduction in seizure frequency whereas a negative percentage change means an increase in seizure frequency.</description>
          <population>Confirmed PK Sample Set from all everolimus-treated patients in the Longer-term Evaluation (LTE) Safety Set, was defined as follows: Cmin collected prior to dose administration on the same treatment day and 20-28 hours after the previous dose, at steady state, and with no evidence of vomiting within 4 hours of the previous dose</population>
          <units>% change over 2-wk in seizures freq.</units>
          <param>Mean</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="0"/>
                <count group_id="O3" value="0"/>
                <count group_id="O4" value="358"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>By doubling the time-normalized Cmin (log scale)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O4" value="8.93" lower_limit="6.87" upper_limit="10.95"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>By reporting half the seizure freq. at baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O4" value="48.82" lower_limit="46.37" upper_limit="51.15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>By adding 12 weeks on treatmen</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O4" value="6.42" lower_limit="4.53" upper_limit="8.27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Core Phase: Impact of Everolimus on Anti-epileptic Drugs (AEDs) Concentrations</title>
        <description>Impact of everolimus on AED concentrations at trough. Pre-dose plasma samples to measure AED concentrations were measured at at Visits 1 (Screening), 2 (Baseline), 3, and 5. Effects of everolimus on the exposure of antiepileptic drugs was assessed by comparing the anti-epileptic drug concentrations at Visits 1 and 2 (AEDs alone) and at Visits 3 and 5 (AEDs plus everolimus).</description>
        <time_frame>Baseline, Weeks 1 &amp; 3</time_frame>
        <population>Confirmed PK Sample Set from all everolimus-treated patients in the Safety Set and Long-term Evaluation (LTE) Safety Set was defined as: Cmin collected prior to dose administration on the same treatment day and 20-28 hours after the previous dose, at steady state, and with no evidence of vomiting within 4 hours of the previous dose.</population>
        <group_list>
          <group group_id="O1">
            <title>Valporic Acid</title>
            <description>Antiepileptic drug</description>
          </group>
          <group group_id="O2">
            <title>Carbamazepine</title>
            <description>antiepileptic drug</description>
          </group>
          <group group_id="O3">
            <title>Clobazam</title>
            <description>antiepileptic drug</description>
          </group>
          <group group_id="O4">
            <title>N-desmethylclobazam</title>
            <description>antiepileptic drug</description>
          </group>
          <group group_id="O5">
            <title>Topiramate</title>
            <description>antiepileptic drug</description>
          </group>
          <group group_id="O6">
            <title>TRI477</title>
            <description>antiepileptic drug</description>
          </group>
          <group group_id="O7">
            <title>TRI476</title>
            <description>antiepileptic drug</description>
          </group>
          <group group_id="O8">
            <title>Clonazepam</title>
            <description>antiepileptic drug</description>
          </group>
          <group group_id="O9">
            <title>Zonisamide</title>
            <description>antiepileptic drug</description>
          </group>
          <group group_id="O10">
            <title>Phenobarbital</title>
            <description>antiepileptic drug</description>
          </group>
          <group group_id="O11">
            <title>Phenytoin</title>
            <description>antiepileptic drug</description>
          </group>
        </group_list>
        <measure>
          <title>Core Phase: Impact of Everolimus on Anti-epileptic Drugs (AEDs) Concentrations</title>
          <description>Impact of everolimus on AED concentrations at trough. Pre-dose plasma samples to measure AED concentrations were measured at at Visits 1 (Screening), 2 (Baseline), 3, and 5. Effects of everolimus on the exposure of antiepileptic drugs was assessed by comparing the anti-epileptic drug concentrations at Visits 1 and 2 (AEDs alone) and at Visits 3 and 5 (AEDs plus everolimus).</description>
          <population>Confirmed PK Sample Set from all everolimus-treated patients in the Safety Set and Long-term Evaluation (LTE) Safety Set was defined as: Cmin collected prior to dose administration on the same treatment day and 20-28 hours after the previous dose, at steady state, and with no evidence of vomiting within 4 hours of the previous dose.</population>
          <units>ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>90% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="86"/>
                <count group_id="O2" value="34"/>
                <count group_id="O3" value="37"/>
                <count group_id="O4" value="37"/>
                <count group_id="O5" value="34"/>
                <count group_id="O6" value="31"/>
                <count group_id="O7" value="31"/>
                <count group_id="O8" value="17"/>
                <count group_id="O9" value="12"/>
                <count group_id="O10" value="11"/>
                <count group_id="O11" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.962" lower_limit="0.913" upper_limit="1.014"/>
                    <measurement group_id="O2" value="1.108" lower_limit="1.016" upper_limit="1.208"/>
                    <measurement group_id="O3" value="1.093" lower_limit="1.037" upper_limit="1.153"/>
                    <measurement group_id="O4" value="1.071" lower_limit="1.017" upper_limit="1.127"/>
                    <measurement group_id="O5" value="0.983" lower_limit="0.872" upper_limit="1.108"/>
                    <measurement group_id="O6" value="1.086" lower_limit="0.913" upper_limit="1.291"/>
                    <measurement group_id="O7" value="1.194" lower_limit="0.936" upper_limit="1.523"/>
                    <measurement group_id="O8" value="1.065" lower_limit="0.974" upper_limit="1.163"/>
                    <measurement group_id="O9" value="1.028" lower_limit="0.971" upper_limit="1.089"/>
                    <measurement group_id="O10" value="0.957" lower_limit="0.886" upper_limit="1.034"/>
                    <measurement group_id="O11" value="1.020" lower_limit="0.874" upper_limit="1.190"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Long Term Evaluation: Percentage Change From Start of Everolimus in Seizure Frequency by Time Window</title>
        <description>Percentage change from start of everolimus in average weekly seizure frequency (SFcfe) = 100 × (SFe - SFtw) ÷ SFe where:&#xD;
SFe is the average weekly seizure frequency in the 8-week period before start of everolimus SFtw is the average weekly seizure frequency in a 12-week time window A positive percentage change from start of everolimus (SFcfe) means a reduction in seizure frequency whereas a negative percentage change from start of everolimus (SFcfe) means an increase in seizure frequency.</description>
        <time_frame>Baseline (8-week period before start of everolimus), Week 7 to 18, Week 19 to 30, and 12 weeks thereafter up to Week 102</time_frame>
        <population>The LTE Efficacy Set included 361 patients who received at least one dose of everolimus in Core and Extension phase and had at least one valid postbaseline efficacy evaluation.</population>
        <group_list>
          <group group_id="O1">
            <title>Everolimus LT Target of 3 to 7 ng/mL</title>
            <description>Participants were randomized to receive everolimus dispersible tablets for oral suspension with titration to a low trough (LT) range of 3 to 7 ng/mL</description>
          </group>
          <group group_id="O2">
            <title>Everolimus HT Target of 9 to 15 ng/mL</title>
            <description>Participants were randomized to receive everolimus dispersible tablets for oral suspension with titration to a high trough (HT) range of 9 to 15 ng/mL</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>Participants were randomized to receive placebo dispersible tablets for oral suspension.</description>
          </group>
          <group group_id="O4">
            <title>Everolimus Long Term Evaluation (LTE)</title>
            <description>Participants who were treated with everolimus either in the Core or Extension phases of the study and were evaluated for longer term safety and efficacy.</description>
          </group>
        </group_list>
        <measure>
          <title>Long Term Evaluation: Percentage Change From Start of Everolimus in Seizure Frequency by Time Window</title>
          <description>Percentage change from start of everolimus in average weekly seizure frequency (SFcfe) = 100 × (SFe - SFtw) ÷ SFe where:&#xD;
SFe is the average weekly seizure frequency in the 8-week period before start of everolimus SFtw is the average weekly seizure frequency in a 12-week time window A positive percentage change from start of everolimus (SFcfe) means a reduction in seizure frequency whereas a negative percentage change from start of everolimus (SFcfe) means an increase in seizure frequency.</description>
          <population>The LTE Efficacy Set included 361 patients who received at least one dose of everolimus in Core and Extension phase and had at least one valid postbaseline efficacy evaluation.</population>
          <units>Percent change</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="0"/>
                <count group_id="O3" value="0"/>
                <count group_id="O4" value="361"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 18</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="0"/>
                    <count group_id="O4" value="352"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O4" value="31.65" lower_limit="28.51" upper_limit="36.09"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 30</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="0"/>
                    <count group_id="O4" value="335"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O4" value="35.74" lower_limit="29.37" upper_limit="39.06"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 42</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="0"/>
                    <count group_id="O4" value="320"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O4" value="42.86" lower_limit="34.44" upper_limit="48.15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 54</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="0"/>
                    <count group_id="O4" value="299"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O4" value="46.05" lower_limit="39.93" upper_limit="53.61"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 66</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="0"/>
                    <count group_id="O4" value="282"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O4" value="49.07" lower_limit="38.26" upper_limit="55.56"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 78</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="0"/>
                    <count group_id="O4" value="252"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O4" value="51.69" lower_limit="43.88" upper_limit="61.58"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 90</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="0"/>
                    <count group_id="O4" value="222"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O4" value="57.33" lower_limit="47.37" upper_limit="67.01"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 102</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="0"/>
                    <count group_id="O4" value="191"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O4" value="59.69" lower_limit="52.13" upper_limit="70.94"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Seizure Free Rates by Time Window</title>
        <description>Percentage of seizure-free participants for each 12-week time window.</description>
        <time_frame>Weeks 18, 30, 42, 54, 66, 78, 90 &amp; 102</time_frame>
        <population>The LTE Efficacy Set included 361 patients who received at least one dose of everolimus in Core and Extension phase and had at least one valid post baseline efficacy evaluation.</population>
        <group_list>
          <group group_id="O1">
            <title>Everolimus LT Target of 3 to 7 ng/mL</title>
            <description>Participants were randomized to receive everolimus dispersible tablets for oral suspension with titration to a low trough (LT) range of 3 to 7 ng/mL</description>
          </group>
          <group group_id="O2">
            <title>Everolimus HT Target of 9 to 15 ng/mL</title>
            <description>Participants were randomized to receive everolimus dispersible tablets for oral suspension with titration to a high trough (HT) range of 9 to 15 ng/mL</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>Participants were randomized to receive placebo dispersible tablets for oral suspension.</description>
          </group>
          <group group_id="O4">
            <title>Everolimus Long Term Evaluation (LTE)</title>
            <description>Participants who were treated with everolimus either in the Core or Extension phases of the study and were evaluated for longer term safety and efficacy.</description>
          </group>
        </group_list>
        <measure>
          <title>Seizure Free Rates by Time Window</title>
          <description>Percentage of seizure-free participants for each 12-week time window.</description>
          <population>The LTE Efficacy Set included 361 patients who received at least one dose of everolimus in Core and Extension phase and had at least one valid post baseline efficacy evaluation.</population>
          <units>Percentage of seizure-free 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="0"/>
                <count group_id="O2" value="0"/>
                <count group_id="O3" value="0"/>
                <count group_id="O4" value="361"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 18</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="0"/>
                    <count group_id="O4" value="352"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O4" value="3.98" lower_limit="2.2" upper_limit="6.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 30</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="0"/>
                    <count group_id="O4" value="335"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O4" value="6.87" lower_limit="4.4" upper_limit="10.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 42</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="0"/>
                    <count group_id="O4" value="320"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O4" value="8.44" lower_limit="5.6" upper_limit="12.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 54</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="0"/>
                    <count group_id="O4" value="299"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O4" value="8.70" lower_limit="5.8" upper_limit="12.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 66</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="0"/>
                    <count group_id="O4" value="282"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O4" value="10.99" lower_limit="7.6" upper_limit="15.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 78</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="0"/>
                    <count group_id="O4" value="252"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O4" value="13.49" lower_limit="9.5" upper_limit="18.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 90</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="0"/>
                    <count group_id="O4" value="222"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O4" value="14.86" lower_limit="10.5" upper_limit="20.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 102</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="0"/>
                    <count group_id="O4" value="191"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O4" value="15.18" lower_limit="10.4" upper_limit="21.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Core Phase: Incidence of Suicide Attempt, Suicidal Ideation or Behavior During Core Phase Per Columbia Suicide Severity Rating Scale (C-SSRS) Outcomes</title>
        <description>Comparison of suicidality using the C-SSRS in the everolimus low-trough treatment arm (3-7 ng/mL), high-trough treatment arm (9-15 ng/mL) and placebo arm. The Columbia-Suicide Severity Rating Scale (C-SSRS) is a questionnaire used for suicide assessment developed by multiple institutions, including Columbia University, with NIMH support. The scale is evidence-supported and is part of a national and international public health initiative involving the assessment of suicidality. There are different scoring systems depending on the population. The important elements to note are that the higher the scores on the individual items and the more &quot;yes&quot; items, the higher the suicide risk.</description>
        <time_frame>Baseline, Week 18</time_frame>
        <population>The Safety Set comprised all patients who received at least one dose of study treatment and had at least one post-Baseline safety assessment in the Core phase (where the statement that a patient had no AE constitutes a safety assessment).</population>
        <group_list>
          <group group_id="O1">
            <title>Everolimus LT Target of 3 to 7 ng/mL</title>
            <description>Participants were randomized to receive everolimus dispersible tablets for oral suspension with titration to a low trough (LT) range of 3 to 7 ng/mL</description>
          </group>
          <group group_id="O2">
            <title>Everolimus HT Target of 9 to 15 ng/mL</title>
            <description>Participants were randomized to receive everolimus dispersible tablets for oral suspension with titration to a high trough (HT) range of 9 to 15 ng/mL</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>Participants were randomized to receive placebo dispersible tablets for oral suspension.</description>
          </group>
        </group_list>
        <measure>
          <title>Core Phase: Incidence of Suicide Attempt, Suicidal Ideation or Behavior During Core Phase Per Columbia Suicide Severity Rating Scale (C-SSRS) Outcomes</title>
          <description>Comparison of suicidality using the C-SSRS in the everolimus low-trough treatment arm (3-7 ng/mL), high-trough treatment arm (9-15 ng/mL) and placebo arm. The Columbia-Suicide Severity Rating Scale (C-SSRS) is a questionnaire used for suicide assessment developed by multiple institutions, including Columbia University, with NIMH support. The scale is evidence-supported and is part of a national and international public health initiative involving the assessment of suicidality. There are different scoring systems depending on the population. The important elements to note are that the higher the scores on the individual items and the more &quot;yes&quot; items, the higher the suicide risk.</description>
          <population>The Safety Set comprised all patients who received at least one dose of study treatment and had at least one post-Baseline safety assessment in the Core phase (where the statement that a patient had no AE constitutes a safety assessment).</population>
          <units>Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="117"/>
                <count group_id="O2" value="130"/>
                <count group_id="O3" value="119"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Completed suicide</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Suicide attempt</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Prep actions toward imminent suicidal behavior</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Suicidal ideation</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Self-injurious behavior without suicide intent</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Long Term Evaluation: Incidence of Suicide Attempt, Suicidal Ideation or Behavior During Core Phase Per Columbia Suicide Severity Rating Scale (C-SSRS) Outcomes</title>
        <description>The C-SSRS was completed at each visit. The table below presents the number of patients who reported at least one completed suicide, one suicide attempt, one preparatory action toward imminent suicidal behavior, one suicidal ideation and one self-injurious behavior without suicidal intent at any time point after starting everolimus.</description>
        <time_frame>During everolimus treatment from start of everolimus up to permanent discontinuation of everolimus, an average of 2.3 years</time_frame>
        <population>The LTE Efficacy Set included 361 patients who received at least one dose of everolimus in Core and Extension phase and had at least one valid post-baseline efficacy evaluation.</population>
        <group_list>
          <group group_id="O1">
            <title>Everolimus LT Target of 3 to 7 ng/mL</title>
            <description>Participants were randomized to receive everolimus dispersible tablets for oral suspension with titration to a low trough (LT) range of 3 to 7 ng/mL</description>
          </group>
          <group group_id="O2">
            <title>Everolimus HT Target of 9 to 15 ng/mL</title>
            <description>Participants were randomized to receive everolimus dispersible tablets for oral suspension with titration to a high trough (HT) range of 9 to 15 ng/mL</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>Participants were randomized to receive placebo dispersible tablets for oral suspension.</description>
          </group>
          <group group_id="O4">
            <title>Everolimus Long Term Evaluation (LTE)</title>
            <description>Participants who were treated with everolimus either in the Core or Extension phases of the study and were evaluated for longer term safety and efficacy.</description>
          </group>
        </group_list>
        <measure>
          <title>Long Term Evaluation: Incidence of Suicide Attempt, Suicidal Ideation or Behavior During Core Phase Per Columbia Suicide Severity Rating Scale (C-SSRS) Outcomes</title>
          <description>The C-SSRS was completed at each visit. The table below presents the number of patients who reported at least one completed suicide, one suicide attempt, one preparatory action toward imminent suicidal behavior, one suicidal ideation and one self-injurious behavior without suicidal intent at any time point after starting everolimus.</description>
          <population>The LTE Efficacy Set included 361 patients who received at least one dose of everolimus in Core and Extension phase and had at least one valid post-baseline efficacy evaluation.</population>
          <units>Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
                <count group_id="O3" value="0"/>
                <count group_id="O4" value="361"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Completed suicide</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Suicidal attempt</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Prep. actions toward imminent suicidal behavior</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O4" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Suicidal ideation</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O4" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Self-injurious behavior without suicide intent</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse Events were collected during everolimus treatment from start of everolimus up to permanent discontinuation of everolimus, an average of 2.3 years</time_frame>
      <desc>The summary tables below include all adverse events starting or worsening on or after the first dose of everolimus, and starting no later than 30 days after the date of last dose of everolimus. Adverse events starting during the placebo period were not counted.</desc>
      <group_list>
        <group group_id="E1">
          <title>Everolimus LT Target of 3 to 7 ng/mL</title>
          <description>Participants were randomized to receive everolimus dispersible tablets for oral suspension with titration to a low trough (LT) range of 3 to 7 ng/mL</description>
        </group>
        <group group_id="E2">
          <title>Everolimus HT Target of 9 to 15 ng/mL</title>
          <description>Participants were randomized to receive everolimus dispersible tablets for oral suspension with titration to a high trough (HT) range of 9 to 15 ng/mL</description>
        </group>
        <group group_id="E3">
          <title>Everolimus Start Ext</title>
          <description>Participants who received placebo dispersible tablets for oral suspension at study start and switched to everolimus in Extension.</description>
        </group>
        <group group_id="E4">
          <title>Everolimus All</title>
          <description>Participants who were treated with everolimus either in the Core or Extension phases of the study and were evaluated for longer term safety and efficacy.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (20.1)</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="1" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="50" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="49" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="38" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="137" subjects_at_risk="361"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Febrile neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Leukocytosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Leukopenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Pancytopenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="361"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Cardiac arrest</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Ear pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Blepharitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Meibomianitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Retinal detachment</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Retinopathy proliferative</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal distension</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="5" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Food poisoning</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Gastric ileus</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Gastrooesophageal reflux disease</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Intestinal ischaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Mouth ulceration</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Stomatitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Swollen tongue</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="361"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="11" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Sudden unexplained death in epilepsy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="361"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Hepatitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaphylactic reaction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Abscess</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Abscess limb</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Appendicitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Bacteraemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="6" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Campylobacter colitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Corona virus infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Croup infectious</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Dacryocanaliculitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Ear infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Febrile infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="14" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Gastroenteritis viral</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Gastrointestinal infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>H1N1 influenza</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Herpangina</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="6" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Lower respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Mastoiditis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Meningitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Oral herpes</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Osteomyelitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Otitis media</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Periorbital cellulitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Perirectal abscess</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Pharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Pharyngitis streptococcal</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="13" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="9" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="38" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Pneumonia bacterial</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Pneumonia influenzal</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Pneumonia mycoplasmal</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Pneumonia viral</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Pseudocroup</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Pyelonephritis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Pyelonephritis acute</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Rotavirus infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Septic shock</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Skin infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Tonsillitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="5" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Tooth abscess</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Tooth infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Urosepsis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Varicella</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Viraemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Viral infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="361"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Craniocerebral injury</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Femur fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Head injury</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Humerus fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Tibia fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Tongue injury</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Toxicity to various agents</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Hepatic enzyme increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Oxygen saturation decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Urine output decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Feeding intolerance</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Hypocalcaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Hypophagia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Hypophosphataemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Ataxia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Dyskinesia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Encephalopathy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Epilepsy</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Febrile convulsion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Generalised tonic-clonic seizure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Ischaemic stroke</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Lethargy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Loss of consciousness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Moyamoya disease</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Seizure</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="18" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Seizure cluster</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Status epilepticus</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="15" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Stupor</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Tremor</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Affect lability</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Aggression</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Confusional state</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Mental status changes</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Mood altered</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Psychotic disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Post streptococcal glomerulonephritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Menorrhagia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Aspiration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Interstitial lung disease</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Lung disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Pneumonia aspiration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Pneumonitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Pulmonary haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Respiratory failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="361"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Erythema nodosum</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Rash generalised</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Skin lesion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Social circumstances</title>
            <event_list>
              <event>
                <sub_title>Sexual abuse</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="361"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA (20.1)</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="110" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="126" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="109" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="345" subjects_at_risk="361"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="21" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="14" subjects_at_risk="361"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="19" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="22" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Aphthous ulcer</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="23" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="10" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="44" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="28" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Dental caries</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="11" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="45" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="42" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="30" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="117" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Mouth ulceration</sub_title>
                <counts group_id="E1" subjects_affected="36" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="44" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="22" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="102" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="16" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Stomatitis</sub_title>
                <counts group_id="E1" subjects_affected="41" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="48" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="41" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="130" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="28" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="35" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="16" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="79" subjects_at_risk="361"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="24" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="47" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="56" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="31" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="134" subjects_at_risk="361"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="17" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="8" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="36" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Conjunctivitis</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="25" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Ear infection</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="19" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="33" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="15" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="35" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Gingivitis</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="13" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Hordeolum</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="15" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="18" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="9" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="43" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Lower respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="10" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="33" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="35" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="26" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="94" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Pharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="18" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="8" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="37" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="9" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Rhinitis</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="23" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="15" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="8" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="26" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Tonsillitis</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="24" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="32" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="42" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="22" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="96" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="28" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Viral infection</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="18" subjects_at_risk="361"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Arthropod bite</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="10" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="16" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="8" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="33" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Laceration</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="13" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Skin abrasion</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="13" subjects_at_risk="361"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood cholesterol increased</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="20" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="17" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="51" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Blood triglycerides increased</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="21" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Low density lipoprotein increased</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="17" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="8" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="25" subjects_at_risk="361"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="20" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="39" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Hyperlipidaemia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="15" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Hypertriglyceridaemia</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="27" subjects_at_risk="361"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="19" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="19" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="10" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="48" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="21" subjects_at_risk="361"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Aggression</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="14" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Agitation</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="10" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="18" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Irritability</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="16" subjects_at_risk="361"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Menstruation irregular</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="11" subjects_at_risk="361"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="29" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="33" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="15" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="77" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="19" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="12" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="20" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Rhinorrhoea</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="22" subjects_at_risk="361"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Acne</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="26" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="14" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Dermatitis</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="11" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="11" subjects_at_risk="361"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="21" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="13" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="48" subjects_at_risk="361"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="117"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="114"/>
                <counts group_id="E4" subjects_affected="19" subjects_at_risk="361"/>
              </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>The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Clinical Disclosure Office</name_or_title>
      <organization>Novartis Pharmaceuticals</organization>
      <phone>862-778-8300</phone>
      <email>novartis.email@novartis.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/NCT01713946
org study id: CRAD001M2304
secondary id: 2011-000860-90
nct id: NCT01713946
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This study evaluated the efficacy and safety of two trough-ranges of everolimus given as
      adjunctive therapy in patients with tuberous sclerosis complex (TSC) who had refractory
      partial-onset seizures.

      The study consisted of 4 phases for each patient Baseline phase:[From Screening Week -8 (V1)
      to randomization visit at Week 0 (V2)], Core phase [from randomization at Week 0 (V2) to Week
      18 (V11)], Extension phase [from Week 18 (V11) until 48 weeks after the last patient had
      completed the core phase] and Post Extension phase [from end of Extension phase to end of
      study].
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Core Phase: European Medicine Agency (EMA): Seizure Frequency Response Rate
time frame: Baseline (8-week period before randomization), Week 7 to 18 (12-week maintenance period of the core phase)
description: Comparison of response rates in the everolimus low-trough treatment arm (3-7 ng/mL), high-trough treatment arm (9-15 ng/mL) and placebo arm. Response means at least a 50% reduction from baseline in partial-onset seizure frequency during the maintenance period of the core phase.
measure: Core Phase: Food & Drug Administration (FDA): Percentage Change From Baseline in Partial Onset-seizure Frequency
time frame: Baseline (8-week period before randomization), Week 7 to 18 (12-week maintenance period of the core phase)
description: Comparison of median percent change from baseline in weekly seizure frequency in the everolimus low-trough treatment arm (3-7 ng/mL), high-trough treatment arm (9-15 ng/mL) and placebo arm during maintenance period of the core phase. Percentage change from baseline in average weekly seizure frequency during the maintenance period of the Core phase (SFcfb) = 100 × (SFB - SFM) ÷ SFB where:
SFB is the average weekly seizure frequency in the Baseline phase SFM is the average weekly seizure frequency in the maintenance period of the Core phase A positive percentage change from baseline (SFcfb) means a reduction in seizure frequency whereas a negative percentage change from baseline (SFcfb) means an increase in seizure frequency.
measure: Percentage of Seizure-free Patients During the Maintenance Period of the Core Phase
time frame: Baseline (8-week period before randomization), Week 7 to 18 (12-week maintenance period of the core phase)
description: Comparison of seizure freedom (100% reduction in seizure frequency) in the everolimus low-trough treatment arm (3-7 ng/mL), high-trough treatment arm (9-15 ng/mL) and placebo arm during maintenance period of the core phase. Seizure free means a 100% reduction from baseline in partial-onset seizure frequency during maintenance period of the core phase.
measure: Core Phase: Percentage of Patients With at Least a 25% Reduction in Seizure Frequency
time frame: Baseline (8-week period before randomization), Week 7 to 18 (12-week maintenance period of the core phase)
description: Comparison of percentage of patients with at least ≥ 25% reduction in seizure frequency in the everolimus low-trough treatment arm (3-7 ng/mL), high-trough treatment arm (9-15 ng/mL) and placebo arm during maintenance period of the core phase. At least 25% reduction from baseline in partial-onset seizure frequency during maintenance period of the core phase.
measure: Core Phase: Distribution of Reduction From Baseline in Seizure Frequency
time frame: Baseline (8-week period before randomization), Week 7 to 18 (12-week maintenance period of the core phase)
description: Comparison of percentage of patients in six categories of seizure reduction from baseline (≤ -25% (exacerbation); > -25% to < 25% (no change); ≥ 25% to < 50%; ≥ 50% to < 75%; ≥ 75% to < 100%; 100% (seizure-freedom)) in the everolimus low-trough treatment arm (3-7 ng/mL), high-trough treatment arm (9-15 ng/mL) and placebo arm during maintenance period of the core phase
measure: Core Phase: Changes From Baseline in Number of Seizure-free Days
time frame: Baseline (8-week period before randomization), Week 7 to 18 (12-week maintenance period of the core phase)
description: Comparison of seizure-free days relative to baseline in the everolimus low-trough treatment arm (3-7 ng/mL), high-trough treatment arm (9-15 ng/mL) and placebo arm during maintenance period of the core phase
measure: Core Phase: Probability That a Patient Remains On-treatment up to a Specified Time Point
time frame: Week 6, Week 12, Week 18
description: Comparison of time to treatment discontinuation in the everolimus low-trough treatment arm (3-7 ng/mL), high-trough treatment arm (9-15 ng/mL) and placebo arm during the core phase. Treatment duration is defined as the time from randomization until the date of permanent study treatment discontinuation (for any reason) at any time during the Core phase.
The percentage event-free probability estimate is the estimated probability that a patient will remain on-treatment up to a specified time point (Week 6, 12, 18)
measure: Core Phase: Change From Baseline in the QOLCE Overall Quality-of-life Score for Patients <11 Years
time frame: Baseline, Week 18
description: Comparison of quality of life in the everolimus (from 3 age specific questionnaires) low-trough treatment arm (3-7 ng/mL), high-trough treatment arm (9-15 ng/mL) and placebo arm at the end of the core phase. The Quality of Life Childhood Epilepsy (QOLCE) questionnaire, used for patients < 11 years at baseline, was completed by the patient's parent or caregiver. It consists of 16 subscales (13 multi-item scales and 3 single item scales) and one overall quality-of-life score. Scores range from 0-100, with higher scores corresponding to improved QoL. The Overall Quality of Life Score is computed by adding each subscale score for each individual and then dividing by 16.
measure: Core Phase: Change From Baseline in the QOLIE-AD-48 Overall Quality-of-life Score for Patients >=11 to 18 Years
time frame: Baseline, Week 18
description: Comparison of quality of life (from 3 age specific questionnaires) in the everolimus low-trough treatment arm (3-7 ng/mL), hightrough treatment arm (9-15 ng/mL) and placebo arm at the end of the core phase. The Quality of Life in Epilepsy Inventory for Adolescents-48 (QOLIE-AD-48) is a survey of health-related quality of life for adolescents 11 to 18 years of age with epilepsy. The QOLIE-AD-48 is completed by the patient. It contains 48 items which assess 8 subscales. Scores range from 0-100, with higher scores corresponding to improved QoL. The overall quality of life score is obtained by summing a linear combination of the 8 subscale scores, where each subscale is multiplied by a relative weight that is provided in the original publication.
measure: Core Phase: Change From Baseline in the QOLIE-31-P Overall Quality-of-life Score for Patients Aged >=18 Years
time frame: Baseline, Week 18
description: Comparison of quality of life (from 3 age specific questionnaires) in the everolimus low-trough treatment arm (3-7 ng/mL), hightrough treatment arm (9-15 ng/mL) and placebo arm at the end of the core phase. The Quality of Life in Epilepsy Inventory-31-Problems (QOLIE-31-P) is a survey of health-related quality of life for adults with epilepsy. The QOLIE-31-P is completed by the patient. It contains 39 items, of which a total of 30 are used to make up 7 different subscales. Scores range from 0-100, with higher scores indicating a greater level of functioning and QoL. The overall quality of life score is obtained by summing a linear combination of the 7 subscale scores, where each subscale is multiplied by a relative weight that is obtained from the patient's answer to 7 items of this questionnaire.
measure: Core Phase: Change From Baseline in the Overall Vineland-II Adaptive Behavior Composite (ABC) Score
time frame: Baseline, 18 weeks
description: Comparison of adaptive functioning using the VABS-II composite score in the everolimus low-trough treatment arm (3-7 ng/mL), high-trough treatment arm (9-15 ng/mL) and placebo arm. The Vineland II assesses an individual's development of personal independence & social responsibility. The questionnaire contains 433 items which assess 15 subdomains organized into the five domains of Communication, Daily Living Skills, Socialization, Motor Skills and Maladaptive Behavior. The overall Adaptive Behavior Composite (ABC) score is obtained by summing the standard scores of the first four domain scores for patients aged less than 7 years, or the first 3 domain scores for patients aged 7 or older (the Maladaptive Behavior domain is optional). The ABC standard score ranges from 20 to 160 with a mean of 100 and a standard deviation of 15. Higher scores correspond to improved adaptive level. Note that 2 questionnaires with ABC scores<20 (data issues) were included in this analysis.
measure: Long Term Evaluation: Effect of Everolimus Over Time in the Overall Vineland-II Adaptive Behavior Composite (ABC) Score
time frame: Baseline, Weeks 18, 42, 66 and 90
description: Comparison of adaptive functioning using the VABS-II composite score in the everolimus low-trough treatment arm (3-7 ng/mL), high-trough treatment arm (9-15 ng/mL) and placebo arm. The Vineland II assesses an individual's development of personal independence & social responsibility. The questionnaire contains 433 items which assess 15 subdomains organized into the five domains of Communication, Daily Living Skills, Socialization, Motor Skills and Maladaptive Behavior. The overall Adaptive Behavior Composite (ABC) score is obtained by summing the standard scores of the first four domain scores for patients aged less than 7 years, or the first 3 domain scores for patients aged 7 or older (the Maladaptive Behavior domain is optional). The ABC standard score ranges from 20 to 160 with a mean of 100 and a standard deviation of 15. Higher scores correspond to improved adaptive level. Note that 2 questionnaires with ABC scores<20 (data issues) were included in this analysis.
measure: Core Phase: Change From Baseline in Wechsler Nonverbal Composite Score
time frame: Baseline, Week 18
description: The brief version of the WNV consists of a 2-subtest battery: only Matrices and Recognition subtests for patients under 8, and Matrices and Spatial Span subtests for patients aged 8 to 21. Based on the raw scores obtained from the subtests, standardized z-scores were calculated for each subtest using the following formula: Zscore = (X - b)/Sb where X is the raw score of the subtest, b and Sb represent the mean and standard deviation respectively of the subtest score recorded at baseline for the study population. The composite WNV score was computed by summing up the Z-scores of the 3 subtests of the WNV (i.e. matrices, recognition, and coding for patients aged <8 years and matrices, spatial span, and coding for patients aged 8 to 21 years). The composite WNV score has no range.
measure: Long Term Evaluation: Effect of Everolimus Over Time in the Overall Wechsler Nonverbal Composite Score
time frame: Baseline, Weeks 18, 42, 66 and 90
description: The brief version of the WNV consists of a 2-subtest battery: only Matrices and Recognition subtests for patients under 8, and Matrices and Spatial Span subtests for patients aged 8 to 21. Based on the raw scores obtained from the subtests, standardized z-scores were calculated for each subtest using the following formula: Zscore = (X - b)/Sb where X is the raw score of the subtest, b and Sb represent the mean and standard deviation respectively of the subtest score recorded at baseline for the study population. The composite WNV score was computed by summing up the Z-scores of the 3 subtests of the WNV (i.e. matrices, recognition, and coding for patients aged <8 years and matrices, spatial span, and coding for patients aged 8 to 21 years). The composite WNV score has no range
measure: Core Phase: Response Rate in Seizure Frequency by Time Normalized Minimum Concentration
time frame: Baseline (8-week period before randomization), Week 7 to 18 (12-week maintenance period of the core phase)
description: Comparison of response rate in seizure frequency for 5 categories of time-normalized minimum concentration (Cmin, TN) (< 3 ng/mL; 3-7 ng/mL; >7-<9 ng/mL; 9-15 ng/mL; >15 ng/mL). Response rate is the percentage of patients with ≥ 50% reduction from baseline in average weekly partial-onset seizure frequency during the maintenance period of the Core phase.
measure: Core Phase: Median Percentage Change From Baseline in Seizure Frequency by Time Normalized Minimum Concentration
time frame: Baseline (8-week period before randomization), Week 7 to 18 (12-week maintenance period of the core phase)
description: Percentage change from baseline in average weekly seizure frequency during the maintenance period of the Core phase is calculated as follow: (SFcfb) = 100 × (SFB - SFM) ÷ SFB where SFB is the average weekly seizure frequency in the Baseline phase and SFM is the average weekly seizure frequency in the maintenance period of the Core phase. A positive percentage change from baseline (SFcfb) means a reduction in seizure frequency whereas a negative percentage change from baseline (SFcfb) means an increase in seizure frequency.
measure: Long Term Evaluation: Relationship Between Seizure Frequency and Time-normalized Everolimus Concentration at Trough (Cmin,TN) - Repeated Measures Analysis
time frame: During everolimus treatment from start of everolimus up to the end of the extension phase, an average of 1.7 year
description: A repeated measures analysis considering fixed 2-week intervals and including the level of exposure (time-normalized Cmin values), the time on-treatment and the seizure frequency at baseline quantified the estimated percentage change over 2 weeks in seizure frequency associated with a double exposure to everolimus, 15 days more on treatment and half the seizure frequency at baseline. A positive percentage change means a reduction in seizure frequency whereas a negative percentage change means an increase in seizure frequency.
measure: Core Phase: Impact of Everolimus on Anti-epileptic Drugs (AEDs) Concentrations
time frame: Baseline, Weeks 1 & 3
description: Impact of everolimus on AED concentrations at trough. Pre-dose plasma samples to measure AED concentrations were measured at at Visits 1 (Screening), 2 (Baseline), 3, and 5. Effects of everolimus on the exposure of antiepileptic drugs was assessed by comparing the anti-epileptic drug concentrations at Visits 1 and 2 (AEDs alone) and at Visits 3 and 5 (AEDs plus everolimus).
measure: Long Term Evaluation: Percentage Change From Start of Everolimus in Seizure Frequency by Time Window
time frame: Baseline (8-week period before start of everolimus), Week 7 to 18, Week 19 to 30, and 12 weeks thereafter up to Week 102
description: Percentage change from start of everolimus in average weekly seizure frequency (SFcfe) = 100 × (SFe - SFtw) ÷ SFe where:
SFe is the average weekly seizure frequency in the 8-week period before start of everolimus SFtw is the average weekly seizure frequency in a 12-week time window A positive percentage change from start of everolimus (SFcfe) means a reduction in seizure frequency whereas a negative percentage change from start of everolimus (SFcfe) means an increase in seizure frequency.
measure: Seizure Free Rates by Time Window
time frame: Weeks 18, 30, 42, 54, 66, 78, 90 & 102
description: Percentage of seizure-free participants for each 12-week time window.
measure: Core Phase: Incidence of Suicide Attempt, Suicidal Ideation or Behavior During Core Phase Per Columbia Suicide Severity Rating Scale (C-SSRS) Outcomes
time frame: Baseline, Week 18
description: Comparison of suicidality using the C-SSRS in the everolimus low-trough treatment arm (3-7 ng/mL), high-trough treatment arm (9-15 ng/mL) and placebo arm. The Columbia-Suicide Severity Rating Scale (C-SSRS) is a questionnaire used for suicide assessment developed by multiple institutions, including Columbia University, with NIMH support. The scale is evidence-supported and is part of a national and international public health initiative involving the assessment of suicidality. There are different scoring systems depending on the population. The important elements to note are that the higher the scores on the individual items and the more "yes" items, the higher the suicide risk.
measure: Long Term Evaluation: Incidence of Suicide Attempt, Suicidal Ideation or Behavior During Core Phase Per Columbia Suicide Severity Rating Scale (C-SSRS) Outcomes
time frame: During everolimus treatment from start of everolimus up to permanent discontinuation of everolimus, an average of 2.3 years
description: The C-SSRS was completed at each visit. The table below presents the number of patients who reported at least one completed suicide, one suicide attempt, one preparatory action toward imminent suicidal behavior, one suicidal ideation and one self-injurious behavior without suicidal intent at any time point after starting everolimus.
arm group label: Everolimus LT target of 3 - 7 ng/mL
arm group type: Experimental
description: Participants received everolimus dispersible tablets for oral suspension with titration to a low trough (LT) range of 3 to 7 ng/mL plus 1 to 3 antiepileptic drugs.
arm group label: Everolimus HT target of 9 -15 ng/mL
arm group type: Experimental
description: Participants received everolimus dispersible tablets for oral suspension with titration to a high trough (HT) range of 9 to 15 ng/mL plus 1 to 3 antiepileptic drugs.
arm group label: Placebo
arm group type: Placebo Comparator
description: Participants received placebo plus 1 to 3 antiepileptic drugs.
intervention type: Drug
intervention name: RAD001
description: Everolimus tablets for oral suspension (dispersible tablets) were packaged as 2 mg tablets in blister packs and placed in boxes with color-coded labels, color 1 or color 2.
arm group label: Everolimus HT target of 9 -15 ng/mL
arm group label: Everolimus LT target of 3 - 7 ng/mL
other name: everolimus
intervention type: Drug
intervention name: Placebo
description: Placebo tablets for oral suspension (dispersible tablets) were packaged as 2 mg tablets in blister packs and placed in boxes with color-coded labels, color 1 or color 2.
arm group label: Placebo
intervention type: Drug
intervention name: Antiepileptic drug (1 to 3 only)
description: no more than any 3 of the listed antiepileptic drugs could be taken with the study drug or placebo. List of allowed antiepileptic drugs were: valporic acid, carbamazepine, clobazam, N-desmethylclobazam, topiramate,TRI477, TRI476, clonazepam, zonisamide, phenobarbital, phenytoin
arm group label: Everolimus HT target of 9 -15 ng/mL
arm group label: Everolimus LT target of 3 - 7 ng/mL
arm group label: Placebo
intervention type: Drug
intervention name: open label RAD001 (only used for post-extension phase)
description: everolimus tablets for oral suspension (dispersible tablets) were packaged as 2 mg tablets in blister backs in boxes with open label design and were taken during the Post-Extension phase, where all the participants, including those who were previously on placebo, took the 2mg tablets.
arm group label: Everolimus HT target of 9 -15 ng/mL
arm group label: Everolimus LT target of 3 - 7 ng/mL
arm group label: Placebo
other name: open label everolimus
criteria: 
gender: All
minimum age: 2 Years
maximum age: 65 Years
healthy volunteers: No
last name: Novartis Pharmaceuticals
role: Study Director
affiliation: Novartis Pharmaceuticals
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country: Argentina
country: Australia
country: Belgium
country: Canada
country: Colombia
country: Denmark
country: France
country: Germany
country: Greece
country: Hungary
country: Ireland
country: Italy
country: Japan
country: Korea, Republic of
country: Mexico
country: Netherlands
country: Norway
country: Poland
country: Russian Federation
country: Spain
country: Taiwan
country: Thailand
country: Turkey
country: United Kingdom
country: United States
country: Sweden
responsible party type: Sponsor
mesh term: Tuberous Sclerosis
mesh term: Seizures
mesh term: Sclerosis
mesh term: Everolimus
mesh term: Anticonvulsants
sharing ipd: Yes
ipd description: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
provided document: 
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outcome list: 
reported events: 
certain agreements: 
point of contact: 