<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02201251</url>
  </required_header>
  <id_info>
    <org_study_id>CR104425</org_study_id>
    <secondary_id>TOPMATEPY4067</secondary_id>
    <secondary_id>2012-001552-19</secondary_id>
    <nct_id>NCT02201251</nct_id>
  </id_info>
  <brief_title>A Study to Investigate the Safety of the Drugs Topiramate and Levetiracetam in Treating Children Recently Diagnosed With Epilepsy</brief_title>
  <official_title>A Randomized, Active-Controlled, Open-Label, Flexible-Dose Study to Assess the Safety and Tolerability of Topiramate as Monotherapy Compared With Levetiracetam as Monotherapy in Pediatric Subjects With New or Recent-Onset Epilepsy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Janssen Research &amp; Development, LLC</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Janssen Research &amp; Development, LLC</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the safety of topiramate monotherapy compared with&#xD;
      levetiracetam another standard antiepileptic drug (AED), as monotherapy for new-onset or&#xD;
      recent-onset epilepsy (seizure disorder) on pediatric growth and maturation, bone&#xD;
      mineralization, and kidney stone formation in children aged 2 to 15 years.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a randomized (study medication assigned to participants by chance), open-label,&#xD;
      multi-centric (conducted in more than one center) and 2-arm flexible-dose monotherapy study&#xD;
      of topiramate compared with 1 another AED (levetiracetam) in pediatric participants with&#xD;
      epilepsy. The total study duration will be up to of 1 year and 2 months per participant. The&#xD;
      study consists of 3 parts: Screening (that is, up to 35 days before study commences on Day&#xD;
      1); Treatment (1 year) and post-treatment (30 days). Safety will primarily be evaluated by&#xD;
      percentage of participants with kidney stones and change from baseline in bone mineral&#xD;
      density at Month 12.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 6, 2014</start_date>
  <completion_date type="Actual">April 30, 2020</completion_date>
  <primary_completion_date type="Actual">April 30, 2020</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Health Services Research</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline in Weight Z-score up to Month 1</measure>
    <time_frame>Baseline up to Month 1</time_frame>
    <description>The Z-Score indicates how many standard deviations (SD) a participant has from the population normal values. The body weight z-scores were designed to take into account the amount of weight gain that was expected due to normal growth in children and adolescents. Body weight data were converted to Z-scores using the Statistical Analysis System (SAS) programs provided by the Centers for Disease Control (CDC) for the calculation of the 2000 CDC growth charts. The mean (SD) change in Z scores from baseline up to Month 1 for the total safety population for all age cohorts combined were presented. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline in Weight Z-score up to Month 3</measure>
    <time_frame>Baseline up to Month 3</time_frame>
    <description>The Z-Score indicates how many SD a participant has from the population normal values. The body weight z-scores were designed to take into account the amount of weight gain that was expected due to normal growth in children and adolescents. Body weight data were converted to Z-scores using the SAS programs provided by the CDC for the calculation of the 2000 CDC growth charts. The mean (SD) change in Z scores from baseline up to Month 3 for the total safety population for all age cohorts combined were presented. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline in Weight Z-score up to Month 6</measure>
    <time_frame>Baseline up to Month 6</time_frame>
    <description>The Z-Score indicates how many SD a participant has from the population normal values. The body weight z-scores were designed to take into account the amount of weight gain that was expected due to normal growth in children and adolescents. Body weight data were converted to Z-scores using the SAS programs provided by the CDC for the calculation of the 2000 CDC growth charts. The mean (SD) change in Z scores from baseline up to Month 6 for the total safety population for all age cohorts combined were presented. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline in Weight Z-score up to Month 9</measure>
    <time_frame>Baseline up to Month 9</time_frame>
    <description>The Z-Score indicates how many SD a participant has from the population normal values. The body weight z-scores were designed to take into account the amount of weight gain that was expected due to normal growth in children and adolescents. Body weight data were converted to Z-scores using the SAS programs provided by the CDC for the calculation of the 2000 CDC growth charts. The mean (SD) change in Z scores from baseline up yo Month 9 for the total safety population for all age cohorts combined were presented. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline in Weight Z-score up to Month 12</measure>
    <time_frame>Baseline up to Month 12</time_frame>
    <description>The Z-Score indicates how many SD a participant has from the population normal values. The body weight z-scores were designed to take into account the amount of weight gain that was expected due to normal growth in children and adolescents. Body weight data were converted to Z-scores using the SAS programs provided by the CDC for the calculation of the 2000 CDC growth charts. The mean (SD) change in Z scores from baseline to Month 12 for the total safety population for all age cohorts combined were presented. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline in Height Z-score up to Month 1</measure>
    <time_frame>Baseline up to Month 1</time_frame>
    <description>Z-Score was a statistical measure to evaluate how a single data point compares to a standard. It described whether a mean was above or below the standard and how unusual the measurement is with range from minus (-) 3 to plus (+) 3; 0 equal to (=) same mean, greater than (&gt;) 0 a greater mean, and less than (&lt;) 0 a lesser mean than the standard. Growth parameters were compared to a standard defined by CDC growth charts. The mean (SD) change in Z scores from baseline up to Month 1 for the total safety population for all age cohorts combined were presented. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline in Height Z-score up to Month 3</measure>
    <time_frame>Baseline up to Month 3</time_frame>
    <description>Z-Score was a statistical measure to evaluate how a single data point compares to a standard. It described whether a mean was above or below the standard and how unusual the measurement is with range from -3 to +3; 0 =same mean, &gt;0 a greater mean, and &lt;0 a lesser mean than the standard. Growth parameters were compared to a standard defined by CDC growth charts. The mean (SD) change in Z scores from baseline up to Month 3 for the total safety population for all age cohorts combined were presented. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline in Height Z-score up to Month 6</measure>
    <time_frame>Baseline up to Month 6</time_frame>
    <description>Z-Score was a statistical measure to evaluate how a single data point compares to a standard. It described whether a mean was above or below the standard and how unusual the measurement is with range from -3 to +3; 0 =same mean, &gt;0 a greater mean, and &lt;0 a lesser mean than the standard. Growth parameters were compared to a standard defined by CDC growth charts. The mean (SD) change in Z scores from baseline up to Month 6 for the total safety population for all age cohorts combined were presented.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline in Height Z-score up to Month 9</measure>
    <time_frame>Baseline up to Month 9</time_frame>
    <description>Z-Score was a statistical measure to evaluate how a single data point compares to a standard. It described whether a mean was above or below the standard and how unusual the measurement is with range from -3 to +3; 0 =same mean, &gt;0 a greater mean, and &lt;0 a lesser mean than the standard. Growth parameters were compared to a standard defined by CDC growth charts. The mean (SD) change in Z scores from baseline up to Month 9 for the total safety population for all age cohorts combined were presented. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline in Height Z-score up to Month 12</measure>
    <time_frame>Baseline up to Month 12</time_frame>
    <description>Z-Score was a statistical measure to evaluate how a single data point compares to a standard. It described whether a mean was above or below the standard and how unusual the measurement is with range from -3 to +3; 0 =same mean, &gt;0 a greater mean, and &lt;0 a lesser mean than the standard. Growth parameters were compared to a standard defined by CDC growth charts. The mean (SD) change in Z scores from baseline up to Month 12 for the total safety population for all age cohorts combined were presented. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline in Bone Mineral Density (BMD) Z-score up to Month 6</measure>
    <time_frame>Baseline up to Month 6</time_frame>
    <description>The BMD was measured by dual energy X-ray absorptiometry (DEXA) for the posterior-anterior lumbar spine (L1_L4) and total body less head area. The Z-Score is the number of standard deviations a participant's BMD differs from the average BMD of their age, sex and ethnicity. Positive scores indicate BMD above the mean; positive values are &quot;best values&quot; and negative values are &quot;worst values&quot;. Positive changes from baseline indicated an improvement in condition.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline in BMD Z-score up to Month 12</measure>
    <time_frame>Baseline up to Month 12</time_frame>
    <description>The BMD was measured by DEXA for the posterior-anterior lumbar spine (L1_L4) and total body less head area. The Z-Score is the number of standard deviations a participant's BMD differs from the average BMD of their age, sex and ethnicity. Positive scores indicate BMD above the mean; positive values are &quot;best values&quot; and negative values are &quot;worst values&quot;. Positive changes from baseline indicated an improvement in condition.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline in Bone Mineral Content (BMC)-Z Score up to Month 6</measure>
    <time_frame>Baseline up to Month 6</time_frame>
    <description>The BMC is an estimate of the amount of mineral (such as calcium) in the bone, which was assessed by DEXA scan for the posterior-anterior lumbar spine (L1_L4) and total body less head area. Positive changes from baseline indicated an improvement in condition.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline in BMC-Z Score up to Month 12</measure>
    <time_frame>Baseline up to Month 12</time_frame>
    <description>The BMC is an estimate of the amount of mineral (such as calcium) in the bone, which was assessed by DEXA scan for the posterior-anterior lumbar spine (L1_L4) and total body less head area. Positive changes from baseline indicated an improvement in condition.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Treatment-emergent Adverse Events (TEAE)</measure>
    <time_frame>Up to Day 390</time_frame>
    <description>An adverse event (AE) is any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. TEAE are defined as AEs with onset during the treatment period or that are a consequence of a pre-existing condition that has worsened since baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Kidney Stones</measure>
    <time_frame>Up to Day 390</time_frame>
    <description>Percentage of participants with kidney stones were reported.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">63</enrollment>
  <condition>Epilepsy</condition>
  <arm_group>
    <arm_group_label>Topiramate</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Topiramate weight based dosing for participants 2 to less than (&lt;) 10 years of age not to exceed 350 mg/day (milligram per day), as tolerated; not to exceed 400 mg/day in participants 10-15 years of age, as tolerated.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Levetiracetam</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Levetiracetam weight based dosing for all participants 2-15 years of age, not to exceed 60 milligram per kilogram per day (mg/kg/day), as tolerated. The maximum recommended daily dosage is 3,000 milligram (mg).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Topiramate</intervention_name>
    <description>Topiramate weight based dosing for participants 2 to &lt;10 years of age not to exceed 350 mg/day, as tolerated; not to exceed 400 mg/day in participants 10-15 years of age, as tolerated.</description>
    <arm_group_label>Topiramate</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Levetiracetam</intervention_name>
    <description>Levetiracetam weight based dosing for all participants 2-15 years of age, not to exceed 60 mg/kg/day, as tolerated. The maximum recommended daily dosage is 3,000 mg.</description>
    <arm_group_label>Levetiracetam</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Participant with a clinical diagnosis of new-onset or recent-onset epilepsy&#xD;
             characterized by partial-onset seizures (POS) (with or without secondary&#xD;
             generalization) or primary generalized tonic-clonic seizures (PGTCS) in accordance&#xD;
             with criteria of the International League Against Epilepsy. The epilepsy diagnosis&#xD;
             must be within the previous 2 years before screening&#xD;
&#xD;
          -  Caregivers (parents or legally acceptable representatives) of the participant must be&#xD;
             able to accurately maintain the participant take-home record and seizure diary&#xD;
&#xD;
          -  At screening, participant must have weight and height values within the 5th to 95th&#xD;
             percentile for chronological age (based on standard Child Height and Weight Charts&#xD;
             from the Centers for Disease Control [CDC])&#xD;
&#xD;
          -  Participant must never have been treated for epilepsy (treatment-naïve) or have been&#xD;
             treated with no more than 1 standard antiepileptic drug (AED) if temporary or urgent&#xD;
             AED use was necessary. Previous AED exposure must not exceed either of the following:&#xD;
             1.)Thirty-one days immediately preceding enrollment, or 2.)A total of 6 months of&#xD;
             previous AED exposure in the past if the AED has been discontinued for at least 1 year&#xD;
             prior to enrollment&#xD;
&#xD;
          -  Parents (or legally acceptable representatives) of the participant must sign an&#xD;
             informed consent/permission document, indicating that they understand the purpose of&#xD;
             and procedures required for the study and are willing to give permission for their&#xD;
             child to participate in the study. Participant 7 years of age and older, capable of&#xD;
             understanding the nature of the study, must provide assent for their participation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Participant has a surgically implanted and functioning vagus nerve stimulator&#xD;
&#xD;
          -  Participant has a history of seizures as a result of a correctable medical condition,&#xD;
             such as metabolic disturbance, toxic exposure, neoplasm, or active infection within 2&#xD;
             weeks prior to the first day of Screening&#xD;
&#xD;
          -  Participant has had uncontrolled seizures while previously taking either topiramate or&#xD;
             levetiracetam&#xD;
&#xD;
          -  Participant has a history of non-epileptic seizures within 2 weeks prior to the first&#xD;
             day of Screening&#xD;
&#xD;
          -  Participant has myoclonic or absence seizures&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>2 Years</minimum_age>
    <maximum_age>15 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Janssen Research &amp; Development, LLC Clinical Trial</last_name>
    <role>Study Director</role>
    <affiliation>Janssen Research &amp; Development, LLC</affiliation>
  </overall_official>
  <location>
    <facility>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Gulf Breeze</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Wellington</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Toledo</city>
        <state>Ohio</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Temple</city>
        <state>Texas</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Buenos Aires</city>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Cordoba</city>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Queensland</city>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Graz</city>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Leuven</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Namur</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Saskatoon</city>
        <state>Saskatchewan</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Brest</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Bron</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Toulouse</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Munchen</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Tübingen</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Balassagyarmat</city>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Budapest N/a</city>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Debrecen</city>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Veszprém</city>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Cebu</city>
        <country>Philippines</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Manila</city>
        <country>Philippines</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Krakow</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Poznan</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Warsaw</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Warszawa</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Saint Petersburg</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Ulyanovsk</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Durban</city>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Kaohsiung</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>New Taipei City</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Taichung</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Taipei</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Argentina</country>
    <country>Australia</country>
    <country>Austria</country>
    <country>Belgium</country>
    <country>Canada</country>
    <country>France</country>
    <country>Germany</country>
    <country>Hungary</country>
    <country>Philippines</country>
    <country>Poland</country>
    <country>Russian Federation</country>
    <country>South Africa</country>
    <country>Taiwan</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>China</country>
    <country>Italy</country>
    <country>Korea, Republic of</country>
    <country>Mexico</country>
    <country>Spain</country>
    <country>Thailand</country>
    <country>United Kingdom</country>
  </removed_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>July 24, 2014</study_first_submitted>
  <study_first_submitted_qc>July 24, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 28, 2014</study_first_posted>
  <results_first_submitted>April 23, 2021</results_first_submitted>
  <results_first_submitted_qc>April 23, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">May 17, 2021</results_first_posted>
  <last_update_submitted>May 1, 2023</last_update_submitted>
  <last_update_submitted_qc>May 1, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 3, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Epilepsy</keyword>
  <keyword>Topiramate</keyword>
  <keyword>Levetiracetam</keyword>
  <keyword>Pediatric</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Epilepsy</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Topiramate</mesh_term>
    <mesh_term>Levetiracetam</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>November 3, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/51/NCT02201251/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>June 8, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/51/NCT02201251/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Topiramate</title>
          <description>Participants received topiramate weight-based sprinkle capsule and tablet, as tolerated (not to exceed 350 milligrams per day [mg/day] for participants 2 to less than [&lt;] 10 years of age, and not to exceed 400 mg/day for participants 10 to 15 years of age), twice daily (BID) for up to 1 year during open-label treatment phase. Participants were to either continue on commercially available topiramate or were tapered off of study drug over a period of up to 2 weeks during post-treatment phase of 30 days.</description>
        </group>
        <group group_id="P2">
          <title>Levetiracetam</title>
          <description>Participants received levetiracetam weight-based tablet or oral solution, as tolerated (not to exceed 60 milligrams per kilogram per day [mg/kg/day] for participants 2 to 15 years of age). The daily dosage was increased every 2 weeks by increments of 20 mg/kg/day to the recommended daily dosage of 60 mg/kg/day. The maximum recommended daily dosage was 3000 mg (1500 mg BID) for up to 1 year during open-label treatment phase. Participants were to either continue on commercially available levetiracetam or were tapered off of study drug over a period of up to 2 weeks during post-treatment phase of 30 days.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="28"/>
                <participants group_id="P2" count="35"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="24"/>
                <participants group_id="P2" count="32"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Noncompliance with Study Drug</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Topiramate</title>
          <description>Participants received topiramate weight-based sprinkle capsule and tablet, as tolerated (not to exceed 350 milligrams per day [mg/day] for participants 2 to less than [&lt;] 10 years of age, and not to exceed 400 mg/day for participants 10 to 15 years of age), twice daily (BID) for up to 1 year during open-label treatment phase. Participants were to either continue on commercially available topiramate or were tapered off of study drug over a period of up to 2 weeks during post-treatment phase of 30 days.</description>
        </group>
        <group group_id="B2">
          <title>Levetiracetam</title>
          <description>Participants received levetiracetam weight-based tablet or oral solution, as tolerated (not to exceed 60 milligrams per kilogram per day [mg/kg/day] for participants 2 to 15 years of age). The daily dosage was increased every 2 weeks by increments of 20 mg/kg/day to the recommended daily dosage of 60 mg/kg/day. The maximum recommended daily dosage was 3000 mg (1500 mg BID) for up to 1 year during open-label treatment phase. Participants were to either continue on commercially available levetiracetam or were tapered off of study drug over a period of up to 2 weeks during post-treatment phase of 30 days.</description>
        </group>
        <group group_id="B3">
          <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="28"/>
            <count group_id="B2" value="35"/>
            <count group_id="B3" value="63"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9.9" spread="2.76"/>
                    <measurement group_id="B2" value="9.3" spread="3.29"/>
                    <measurement group_id="B3" value="9.6" spread="3.05"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="18"/>
                    <measurement group_id="B3" value="34"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="20"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="25"/>
                    <measurement group_id="B3" value="43"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>AUSTRIA</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>CANADA</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>HUNGARY</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ITALY</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>PHILIPPINES</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>POLAND</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>RUSSIAN FEDERATION</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TAIWAN</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>UNITED STATES</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Weight Z-score up to Month 1</title>
        <description>The Z-Score indicates how many standard deviations (SD) a participant has from the population normal values. The body weight z-scores were designed to take into account the amount of weight gain that was expected due to normal growth in children and adolescents. Body weight data were converted to Z-scores using the Statistical Analysis System (SAS) programs provided by the Centers for Disease Control (CDC) for the calculation of the 2000 CDC growth charts. The mean (SD) change in Z scores from baseline up to Month 1 for the total safety population for all age cohorts combined were presented. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.</description>
        <time_frame>Baseline up to Month 1</time_frame>
        <population>The safety analysis set included all randomized participants who received at least 1 dose of study drug. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Topiramate</title>
            <description>Participants received topiramate weight-based sprinkle capsule and tablet, as tolerated (not to exceed 350 milligrams per day [mg/day] for participants 2 to less than [&lt;] 10 years of age, and not to exceed 400 mg/day for participants 10 to 15 years of age), twice daily (BID) for up to 1 year during open-label treatment phase. Participants were to either continue on commercially available topiramate or were tapered off of study drug over a period of up to 2 weeks during post-treatment phase of 30 days.</description>
          </group>
          <group group_id="O2">
            <title>Levetiracetam</title>
            <description>Participants received levetiracetam weight-based tablet or oral solution, as tolerated (not to exceed 60 milligrams per kilogram per day [mg/kg/day] for participants 2 to 15 years of age). The daily dosage was increased every 2 weeks by increments of 20 mg/kg/day to the recommended daily dosage of 60 mg/kg/day. The maximum recommended daily dosage was 3000 mg (1500 mg BID) for up to 1 year during open-label treatment phase. Participants were to either continue on commercially available levetiracetam or were tapered off of study drug over a period of up to 2 weeks during post-treatment phase of 30 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Weight Z-score up to Month 1</title>
          <description>The Z-Score indicates how many standard deviations (SD) a participant has from the population normal values. The body weight z-scores were designed to take into account the amount of weight gain that was expected due to normal growth in children and adolescents. Body weight data were converted to Z-scores using the Statistical Analysis System (SAS) programs provided by the Centers for Disease Control (CDC) for the calculation of the 2000 CDC growth charts. The mean (SD) change in Z scores from baseline up to Month 1 for the total safety population for all age cohorts combined were presented. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.</description>
          <population>The safety analysis set included all randomized participants who received at least 1 dose of study drug. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure.</population>
          <units>Z-score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="27"/>
                <count group_id="O2" value="34"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.112" spread="0.1220" lower_limit="0.1220"/>
                    <measurement group_id="O2" value="-0.014" spread="0.1244" lower_limit="0.1244"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Weight Z-score up to Month 3</title>
        <description>The Z-Score indicates how many SD a participant has from the population normal values. The body weight z-scores were designed to take into account the amount of weight gain that was expected due to normal growth in children and adolescents. Body weight data were converted to Z-scores using the SAS programs provided by the CDC for the calculation of the 2000 CDC growth charts. The mean (SD) change in Z scores from baseline up to Month 3 for the total safety population for all age cohorts combined were presented. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.</description>
        <time_frame>Baseline up to Month 3</time_frame>
        <population>The safety analysis set included all randomized participants who received at least 1 dose of study drug. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Topiramate</title>
            <description>Participants received topiramate weight-based sprinkle capsule and tablet, as tolerated (not to exceed 350 milligrams per day [mg/day] for participants 2 to less than [&lt;] 10 years of age, and not to exceed 400 mg/day for participants 10 to 15 years of age), twice daily (BID) for up to 1 year during open-label treatment phase. Participants were to either continue on commercially available topiramate or were tapered off of study drug over a period of up to 2 weeks during post-treatment phase of 30 days.</description>
          </group>
          <group group_id="O2">
            <title>Levetiracetam</title>
            <description>Participants received levetiracetam weight-based tablet or oral solution, as tolerated (not to exceed 60 milligrams per kilogram per day [mg/kg/day] for participants 2 to 15 years of age). The daily dosage was increased every 2 weeks by increments of 20 mg/kg/day to the recommended daily dosage of 60 mg/kg/day. The maximum recommended daily dosage was 3000 mg (1500 mg BID) for up to 1 year during open-label treatment phase. Participants were to either continue on commercially available levetiracetam or were tapered off of study drug over a period of up to 2 weeks during post-treatment phase of 30 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Weight Z-score up to Month 3</title>
          <description>The Z-Score indicates how many SD a participant has from the population normal values. The body weight z-scores were designed to take into account the amount of weight gain that was expected due to normal growth in children and adolescents. Body weight data were converted to Z-scores using the SAS programs provided by the CDC for the calculation of the 2000 CDC growth charts. The mean (SD) change in Z scores from baseline up to Month 3 for the total safety population for all age cohorts combined were presented. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.</description>
          <population>The safety analysis set included all randomized participants who received at least 1 dose of study drug. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure.</population>
          <units>Z-score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="27"/>
                <count group_id="O2" value="34"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.201" spread="0.2094" lower_limit="0.2094"/>
                    <measurement group_id="O2" value="-0.027" spread="0.1802" lower_limit="0.1802"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Weight Z-score up to Month 6</title>
        <description>The Z-Score indicates how many SD a participant has from the population normal values. The body weight z-scores were designed to take into account the amount of weight gain that was expected due to normal growth in children and adolescents. Body weight data were converted to Z-scores using the SAS programs provided by the CDC for the calculation of the 2000 CDC growth charts. The mean (SD) change in Z scores from baseline up to Month 6 for the total safety population for all age cohorts combined were presented. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.</description>
        <time_frame>Baseline up to Month 6</time_frame>
        <population>The safety analysis set included all randomized participants who received at least 1 dose of study drug. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Topiramate</title>
            <description>Participants received topiramate weight-based sprinkle capsule and tablet, as tolerated (not to exceed 350 milligrams per day [mg/day] for participants 2 to less than [&lt;] 10 years of age, and not to exceed 400 mg/day for participants 10 to 15 years of age), twice daily (BID) for up to 1 year during open-label treatment phase. Participants were to either continue on commercially available topiramate or were tapered off of study drug over a period of up to 2 weeks during post-treatment phase of 30 days.</description>
          </group>
          <group group_id="O2">
            <title>Levetiracetam</title>
            <description>Participants received levetiracetam weight-based tablet or oral solution, as tolerated (not to exceed 60 milligrams per kilogram per day [mg/kg/day] for participants 2 to 15 years of age). The daily dosage was increased every 2 weeks by increments of 20 mg/kg/day to the recommended daily dosage of 60 mg/kg/day. The maximum recommended daily dosage was 3000 mg (1500 mg BID) for up to 1 year during open-label treatment phase. Participants were to either continue on commercially available levetiracetam or were tapered off of study drug over a period of up to 2 weeks during post-treatment phase of 30 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Weight Z-score up to Month 6</title>
          <description>The Z-Score indicates how many SD a participant has from the population normal values. The body weight z-scores were designed to take into account the amount of weight gain that was expected due to normal growth in children and adolescents. Body weight data were converted to Z-scores using the SAS programs provided by the CDC for the calculation of the 2000 CDC growth charts. The mean (SD) change in Z scores from baseline up to Month 6 for the total safety population for all age cohorts combined were presented. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.</description>
          <population>The safety analysis set included all randomized participants who received at least 1 dose of study drug. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure.</population>
          <units>Z-score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="24"/>
                <count group_id="O2" value="33"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.319" spread="0.2496" lower_limit="0.2496"/>
                    <measurement group_id="O2" value="-0.070" spread="0.2304" lower_limit="0.2304"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Weight Z-score up to Month 9</title>
        <description>The Z-Score indicates how many SD a participant has from the population normal values. The body weight z-scores were designed to take into account the amount of weight gain that was expected due to normal growth in children and adolescents. Body weight data were converted to Z-scores using the SAS programs provided by the CDC for the calculation of the 2000 CDC growth charts. The mean (SD) change in Z scores from baseline up yo Month 9 for the total safety population for all age cohorts combined were presented. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.</description>
        <time_frame>Baseline up to Month 9</time_frame>
        <population>The safety analysis set included all randomized participants who received at least 1 dose of study drug. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Topiramate</title>
            <description>Participants received topiramate weight-based sprinkle capsule and tablet, as tolerated (not to exceed 350 milligrams per day [mg/day] for participants 2 to less than [&lt;] 10 years of age, and not to exceed 400 mg/day for participants 10 to 15 years of age), twice daily (BID) for up to 1 year during open-label treatment phase. Participants were to either continue on commercially available topiramate or were tapered off of study drug over a period of up to 2 weeks during post-treatment phase of 30 days.</description>
          </group>
          <group group_id="O2">
            <title>Levetiracetam</title>
            <description>Participants received levetiracetam weight-based tablet or oral solution, as tolerated (not to exceed 60 milligrams per kilogram per day [mg/kg/day] for participants 2 to 15 years of age). The daily dosage was increased every 2 weeks by increments of 20 mg/kg/day to the recommended daily dosage of 60 mg/kg/day. The maximum recommended daily dosage was 3000 mg (1500 mg BID) for up to 1 year during open-label treatment phase. Participants were to either continue on commercially available levetiracetam or were tapered off of study drug over a period of up to 2 weeks during post-treatment phase of 30 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Weight Z-score up to Month 9</title>
          <description>The Z-Score indicates how many SD a participant has from the population normal values. The body weight z-scores were designed to take into account the amount of weight gain that was expected due to normal growth in children and adolescents. Body weight data were converted to Z-scores using the SAS programs provided by the CDC for the calculation of the 2000 CDC growth charts. The mean (SD) change in Z scores from baseline up yo Month 9 for the total safety population for all age cohorts combined were presented. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.</description>
          <population>The safety analysis set included all randomized participants who received at least 1 dose of study drug. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure.</population>
          <units>Z-score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="24"/>
                <count group_id="O2" value="32"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.326" spread="0.3235" lower_limit="0.3235"/>
                    <measurement group_id="O2" value="-0.110" spread="0.3584" lower_limit="0.3584"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Weight Z-score up to Month 12</title>
        <description>The Z-Score indicates how many SD a participant has from the population normal values. The body weight z-scores were designed to take into account the amount of weight gain that was expected due to normal growth in children and adolescents. Body weight data were converted to Z-scores using the SAS programs provided by the CDC for the calculation of the 2000 CDC growth charts. The mean (SD) change in Z scores from baseline to Month 12 for the total safety population for all age cohorts combined were presented. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.</description>
        <time_frame>Baseline up to Month 12</time_frame>
        <population>The safety analysis set included all randomized participants who received at least 1 dose of study drug. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Topiramate</title>
            <description>Participants received topiramate weight-based sprinkle capsule and tablet, as tolerated (not to exceed 350 milligrams per day [mg/day] for participants 2 to less than [&lt;] 10 years of age, and not to exceed 400 mg/day for participants 10 to 15 years of age), twice daily (BID) for up to 1 year during open-label treatment phase. Participants were to either continue on commercially available topiramate or were tapered off of study drug over a period of up to 2 weeks during post-treatment phase of 30 days.</description>
          </group>
          <group group_id="O2">
            <title>Levetiracetam</title>
            <description>Participants received levetiracetam weight-based tablet or oral solution, as tolerated (not to exceed 60 milligrams per kilogram per day [mg/kg/day] for participants 2 to 15 years of age). The daily dosage was increased every 2 weeks by increments of 20 mg/kg/day to the recommended daily dosage of 60 mg/kg/day. The maximum recommended daily dosage was 3000 mg (1500 mg BID) for up to 1 year during open-label treatment phase. Participants were to either continue on commercially available levetiracetam or were tapered off of study drug over a period of up to 2 weeks during post-treatment phase of 30 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Weight Z-score up to Month 12</title>
          <description>The Z-Score indicates how many SD a participant has from the population normal values. The body weight z-scores were designed to take into account the amount of weight gain that was expected due to normal growth in children and adolescents. Body weight data were converted to Z-scores using the SAS programs provided by the CDC for the calculation of the 2000 CDC growth charts. The mean (SD) change in Z scores from baseline to Month 12 for the total safety population for all age cohorts combined were presented. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.</description>
          <population>The safety analysis set included all randomized participants who received at least 1 dose of study drug. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure.</population>
          <units>Z-score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="24"/>
                <count group_id="O2" value="32"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.351" spread="0.3905" lower_limit="0.3905"/>
                    <measurement group_id="O2" value="-0.065" spread="0.3026" lower_limit="0.3026"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Height Z-score up to Month 1</title>
        <description>Z-Score was a statistical measure to evaluate how a single data point compares to a standard. It described whether a mean was above or below the standard and how unusual the measurement is with range from minus (-) 3 to plus (+) 3; 0 equal to (=) same mean, greater than (&gt;) 0 a greater mean, and less than (&lt;) 0 a lesser mean than the standard. Growth parameters were compared to a standard defined by CDC growth charts. The mean (SD) change in Z scores from baseline up to Month 1 for the total safety population for all age cohorts combined were presented. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.</description>
        <time_frame>Baseline up to Month 1</time_frame>
        <population>The safety analysis set included all randomized participants who received at least 1 dose of study drug. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Topiramate</title>
            <description>Participants received topiramate weight-based sprinkle capsule and tablet, as tolerated (not to exceed 350 milligrams per day [mg/day] for participants 2 to less than [&lt;] 10 years of age, and not to exceed 400 mg/day for participants 10 to 15 years of age), twice daily (BID) for up to 1 year during open-label treatment phase. Participants were to either continue on commercially available topiramate or were tapered off of study drug over a period of up to 2 weeks during post-treatment phase of 30 days.</description>
          </group>
          <group group_id="O2">
            <title>Levetiracetam</title>
            <description>Participants received levetiracetam weight-based tablet or oral solution, as tolerated (not to exceed 60 milligrams per kilogram per day [mg/kg/day] for participants 2 to 15 years of age). The daily dosage was increased every 2 weeks by increments of 20 mg/kg/day to the recommended daily dosage of 60 mg/kg/day. The maximum recommended daily dosage was 3000 mg (1500 mg BID) for up to 1 year during open-label treatment phase. Participants were to either continue on commercially available levetiracetam or were tapered off of study drug over a period of up to 2 weeks during post-treatment phase of 30 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Height Z-score up to Month 1</title>
          <description>Z-Score was a statistical measure to evaluate how a single data point compares to a standard. It described whether a mean was above or below the standard and how unusual the measurement is with range from minus (-) 3 to plus (+) 3; 0 equal to (=) same mean, greater than (&gt;) 0 a greater mean, and less than (&lt;) 0 a lesser mean than the standard. Growth parameters were compared to a standard defined by CDC growth charts. The mean (SD) change in Z scores from baseline up to Month 1 for the total safety population for all age cohorts combined were presented. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.</description>
          <population>The safety analysis set included all randomized participants who received at least 1 dose of study drug. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure.</population>
          <units>Z-score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="27"/>
                <count group_id="O2" value="33"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.004" spread="0.0870" lower_limit="0.0870"/>
                    <measurement group_id="O2" value="-0.015" spread="0.1017" lower_limit="0.1017"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Height Z-score up to Month 3</title>
        <description>Z-Score was a statistical measure to evaluate how a single data point compares to a standard. It described whether a mean was above or below the standard and how unusual the measurement is with range from -3 to +3; 0 =same mean, &gt;0 a greater mean, and &lt;0 a lesser mean than the standard. Growth parameters were compared to a standard defined by CDC growth charts. The mean (SD) change in Z scores from baseline up to Month 3 for the total safety population for all age cohorts combined were presented. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.</description>
        <time_frame>Baseline up to Month 3</time_frame>
        <population>The safety analysis set included all randomized participants who received at least 1 dose of study drug. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Topiramate</title>
            <description>Participants received topiramate weight-based sprinkle capsule and tablet, as tolerated (not to exceed 350 milligrams per day [mg/day] for participants 2 to less than [&lt;] 10 years of age, and not to exceed 400 mg/day for participants 10 to 15 years of age), twice daily (BID) for up to 1 year during open-label treatment phase. Participants were to either continue on commercially available topiramate or were tapered off of study drug over a period of up to 2 weeks during post-treatment phase of 30 days.</description>
          </group>
          <group group_id="O2">
            <title>Levetiracetam</title>
            <description>Participants received levetiracetam weight-based tablet or oral solution, as tolerated (not to exceed 60 milligrams per kilogram per day [mg/kg/day] for participants 2 to 15 years of age). The daily dosage was increased every 2 weeks by increments of 20 mg/kg/day to the recommended daily dosage of 60 mg/kg/day. The maximum recommended daily dosage was 3000 mg (1500 mg BID) for up to 1 year during open-label treatment phase. Participants were to either continue on commercially available levetiracetam or were tapered off of study drug over a period of up to 2 weeks during post-treatment phase of 30 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Height Z-score up to Month 3</title>
          <description>Z-Score was a statistical measure to evaluate how a single data point compares to a standard. It described whether a mean was above or below the standard and how unusual the measurement is with range from -3 to +3; 0 =same mean, &gt;0 a greater mean, and &lt;0 a lesser mean than the standard. Growth parameters were compared to a standard defined by CDC growth charts. The mean (SD) change in Z scores from baseline up to Month 3 for the total safety population for all age cohorts combined were presented. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.</description>
          <population>The safety analysis set included all randomized participants who received at least 1 dose of study drug. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure.</population>
          <units>Z-score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="27"/>
                <count group_id="O2" value="34"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.036" spread="0.1452" lower_limit="0.1452"/>
                    <measurement group_id="O2" value="0.017" spread="0.1631" lower_limit="0.1631"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Height Z-score up to Month 6</title>
        <description>Z-Score was a statistical measure to evaluate how a single data point compares to a standard. It described whether a mean was above or below the standard and how unusual the measurement is with range from -3 to +3; 0 =same mean, &gt;0 a greater mean, and &lt;0 a lesser mean than the standard. Growth parameters were compared to a standard defined by CDC growth charts. The mean (SD) change in Z scores from baseline up to Month 6 for the total safety population for all age cohorts combined were presented.</description>
        <time_frame>Baseline up to Month 6</time_frame>
        <population>The safety analysis set included all randomized participants who received at least 1 dose of study drug. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Topiramate</title>
            <description>Participants received topiramate weight-based sprinkle capsule and tablet, as tolerated (not to exceed 350 milligrams per day [mg/day] for participants 2 to less than [&lt;] 10 years of age, and not to exceed 400 mg/day for participants 10 to 15 years of age), twice daily (BID) for up to 1 year during open-label treatment phase. Participants were to either continue on commercially available topiramate or were tapered off of study drug over a period of up to 2 weeks during post-treatment phase of 30 days.</description>
          </group>
          <group group_id="O2">
            <title>Levetiracetam</title>
            <description>Participants received levetiracetam weight-based tablet or oral solution, as tolerated (not to exceed 60 milligrams per kilogram per day [mg/kg/day] for participants 2 to 15 years of age). The daily dosage was increased every 2 weeks by increments of 20 mg/kg/day to the recommended daily dosage of 60 mg/kg/day. The maximum recommended daily dosage was 3000 mg (1500 mg BID) for up to 1 year during open-label treatment phase. Participants were to either continue on commercially available levetiracetam or were tapered off of study drug over a period of up to 2 weeks during post-treatment phase of 30 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Height Z-score up to Month 6</title>
          <description>Z-Score was a statistical measure to evaluate how a single data point compares to a standard. It described whether a mean was above or below the standard and how unusual the measurement is with range from -3 to +3; 0 =same mean, &gt;0 a greater mean, and &lt;0 a lesser mean than the standard. Growth parameters were compared to a standard defined by CDC growth charts. The mean (SD) change in Z scores from baseline up to Month 6 for the total safety population for all age cohorts combined were presented.</description>
          <population>The safety analysis set included all randomized participants who received at least 1 dose of study drug. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure.</population>
          <units>Z-score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="24"/>
                <count group_id="O2" value="33"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.008" spread="0.1753" lower_limit="0.1753"/>
                    <measurement group_id="O2" value="0.077" spread="0.2670" lower_limit="0.2670"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Height Z-score up to Month 9</title>
        <description>Z-Score was a statistical measure to evaluate how a single data point compares to a standard. It described whether a mean was above or below the standard and how unusual the measurement is with range from -3 to +3; 0 =same mean, &gt;0 a greater mean, and &lt;0 a lesser mean than the standard. Growth parameters were compared to a standard defined by CDC growth charts. The mean (SD) change in Z scores from baseline up to Month 9 for the total safety population for all age cohorts combined were presented. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.</description>
        <time_frame>Baseline up to Month 9</time_frame>
        <population>The safety analysis set included all randomized participants who received at least 1 dose of study drug. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Topiramate</title>
            <description>Participants received topiramate weight-based sprinkle capsule and tablet, as tolerated (not to exceed 350 milligrams per day [mg/day] for participants 2 to less than [&lt;] 10 years of age, and not to exceed 400 mg/day for participants 10 to 15 years of age), twice daily (BID) for up to 1 year during open-label treatment phase. Participants were to either continue on commercially available topiramate or were tapered off of study drug over a period of up to 2 weeks during post-treatment phase of 30 days.</description>
          </group>
          <group group_id="O2">
            <title>Levetiracetam</title>
            <description>Participants received levetiracetam weight-based tablet or oral solution, as tolerated (not to exceed 60 milligrams per kilogram per day [mg/kg/day] for participants 2 to 15 years of age). The daily dosage was increased every 2 weeks by increments of 20 mg/kg/day to the recommended daily dosage of 60 mg/kg/day. The maximum recommended daily dosage was 3000 mg (1500 mg BID) for up to 1 year during open-label treatment phase. Participants were to either continue on commercially available levetiracetam or were tapered off of study drug over a period of up to 2 weeks during post-treatment phase of 30 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Height Z-score up to Month 9</title>
          <description>Z-Score was a statistical measure to evaluate how a single data point compares to a standard. It described whether a mean was above or below the standard and how unusual the measurement is with range from -3 to +3; 0 =same mean, &gt;0 a greater mean, and &lt;0 a lesser mean than the standard. Growth parameters were compared to a standard defined by CDC growth charts. The mean (SD) change in Z scores from baseline up to Month 9 for the total safety population for all age cohorts combined were presented. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.</description>
          <population>The safety analysis set included all randomized participants who received at least 1 dose of study drug. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure.</population>
          <units>Z-score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="24"/>
                <count group_id="O2" value="32"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.059" spread="0.2337" lower_limit="0.2337"/>
                    <measurement group_id="O2" value="0.086" spread="0.2929" lower_limit="0.2929"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Height Z-score up to Month 12</title>
        <description>Z-Score was a statistical measure to evaluate how a single data point compares to a standard. It described whether a mean was above or below the standard and how unusual the measurement is with range from -3 to +3; 0 =same mean, &gt;0 a greater mean, and &lt;0 a lesser mean than the standard. Growth parameters were compared to a standard defined by CDC growth charts. The mean (SD) change in Z scores from baseline up to Month 12 for the total safety population for all age cohorts combined were presented. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.</description>
        <time_frame>Baseline up to Month 12</time_frame>
        <population>The safety analysis set included all randomized participants who received at least 1 dose of study drug. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Topiramate</title>
            <description>Participants received topiramate weight-based sprinkle capsule and tablet, as tolerated (not to exceed 350 milligrams per day [mg/day] for participants 2 to less than [&lt;] 10 years of age, and not to exceed 400 mg/day for participants 10 to 15 years of age), twice daily (BID) for up to 1 year during open-label treatment phase. Participants were to either continue on commercially available topiramate or were tapered off of study drug over a period of up to 2 weeks during post-treatment phase of 30 days.</description>
          </group>
          <group group_id="O2">
            <title>Levetiracetam</title>
            <description>Participants received levetiracetam weight-based tablet or oral solution, as tolerated (not to exceed 60 milligrams per kilogram per day [mg/kg/day] for participants 2 to 15 years of age). The daily dosage was increased every 2 weeks by increments of 20 mg/kg/day to the recommended daily dosage of 60 mg/kg/day. The maximum recommended daily dosage was 3000 mg (1500 mg BID) for up to 1 year during open-label treatment phase. Participants were to either continue on commercially available levetiracetam or were tapered off of study drug over a period of up to 2 weeks during post-treatment phase of 30 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Height Z-score up to Month 12</title>
          <description>Z-Score was a statistical measure to evaluate how a single data point compares to a standard. It described whether a mean was above or below the standard and how unusual the measurement is with range from -3 to +3; 0 =same mean, &gt;0 a greater mean, and &lt;0 a lesser mean than the standard. Growth parameters were compared to a standard defined by CDC growth charts. The mean (SD) change in Z scores from baseline up to Month 12 for the total safety population for all age cohorts combined were presented. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.</description>
          <population>The safety analysis set included all randomized participants who received at least 1 dose of study drug. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure.</population>
          <units>Z-score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="24"/>
                <count group_id="O2" value="32"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.057" spread="0.2734" lower_limit="0.2734"/>
                    <measurement group_id="O2" value="0.088" spread="0.3315" lower_limit="0.3315"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Bone Mineral Density (BMD) Z-score up to Month 6</title>
        <description>The BMD was measured by dual energy X-ray absorptiometry (DEXA) for the posterior-anterior lumbar spine (L1_L4) and total body less head area. The Z-Score is the number of standard deviations a participant's BMD differs from the average BMD of their age, sex and ethnicity. Positive scores indicate BMD above the mean; positive values are &quot;best values&quot; and negative values are &quot;worst values&quot;. Positive changes from baseline indicated an improvement in condition.</description>
        <time_frame>Baseline up to Month 6</time_frame>
        <population>The safety analysis set included all randomized participants who received at least 1 dose of study drug. Here 'N' (number of participants analyzed) signifies the number of participants evaluable for this outcome measure. Here, 'n' (number analyzed) signifies the number of participants evaluable for specified categories.</population>
        <group_list>
          <group group_id="O1">
            <title>Topiramate</title>
            <description>Participants received topiramate weight-based sprinkle capsule and tablet, as tolerated (not to exceed 350 milligrams per day [mg/day] for participants 2 to less than [&lt;] 10 years of age, and not to exceed 400 mg/day for participants 10 to 15 years of age), twice daily (BID) for up to 1 year during open-label treatment phase. Participants were to either continue on commercially available topiramate or were tapered off of study drug over a period of up to 2 weeks during post-treatment phase of 30 days.</description>
          </group>
          <group group_id="O2">
            <title>Levetiracetam</title>
            <description>Participants received levetiracetam weight-based tablet or oral solution, as tolerated (not to exceed 60 milligrams per kilogram per day [mg/kg/day] for participants 2 to 15 years of age). The daily dosage was increased every 2 weeks by increments of 20 mg/kg/day to the recommended daily dosage of 60 mg/kg/day. The maximum recommended daily dosage was 3000 mg (1500 mg BID) for up to 1 year during open-label treatment phase. Participants were to either continue on commercially available levetiracetam or were tapered off of study drug over a period of up to 2 weeks during post-treatment phase of 30 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Bone Mineral Density (BMD) Z-score up to Month 6</title>
          <description>The BMD was measured by dual energy X-ray absorptiometry (DEXA) for the posterior-anterior lumbar spine (L1_L4) and total body less head area. The Z-Score is the number of standard deviations a participant's BMD differs from the average BMD of their age, sex and ethnicity. Positive scores indicate BMD above the mean; positive values are &quot;best values&quot; and negative values are &quot;worst values&quot;. Positive changes from baseline indicated an improvement in condition.</description>
          <population>The safety analysis set included all randomized participants who received at least 1 dose of study drug. Here 'N' (number of participants analyzed) signifies the number of participants evaluable for this outcome measure. Here, 'n' (number analyzed) signifies the number of participants evaluable for specified categories.</population>
          <units>Z-score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="32"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Lumbar spine</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="24"/>
                    <count group_id="O2" value="32"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.181" spread="0.2590"/>
                    <measurement group_id="O2" value="0.035" spread="0.2606"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Total body less head</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="25"/>
                    <count group_id="O2" value="30"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.180" spread="0.2647"/>
                    <measurement group_id="O2" value="0.102" spread="0.2574"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in BMD Z-score up to Month 12</title>
        <description>The BMD was measured by DEXA for the posterior-anterior lumbar spine (L1_L4) and total body less head area. The Z-Score is the number of standard deviations a participant's BMD differs from the average BMD of their age, sex and ethnicity. Positive scores indicate BMD above the mean; positive values are &quot;best values&quot; and negative values are &quot;worst values&quot;. Positive changes from baseline indicated an improvement in condition.</description>
        <time_frame>Baseline up to Month 12</time_frame>
        <population>The safety analysis set included all randomized participants who received at least 1 dose of study drug. Here 'N' (number of participants analyzed) signifies the number of participants evaluable for this outcome measure. Here, 'n' (number analyzed) signifies the number of participants evaluable at a specified category.</population>
        <group_list>
          <group group_id="O1">
            <title>Topiramate</title>
            <description>Participants received topiramate weight-based sprinkle capsule and tablet, as tolerated (not to exceed 350 milligrams per day [mg/day] for participants 2 to less than [&lt;] 10 years of age, and not to exceed 400 mg/day for participants 10 to 15 years of age), twice daily (BID) for up to 1 year during open-label treatment phase. Participants were to either continue on commercially available topiramate or were tapered off of study drug over a period of up to 2 weeks during post-treatment phase of 30 days.</description>
          </group>
          <group group_id="O2">
            <title>Levetiracetam</title>
            <description>Participants received levetiracetam weight-based tablet or oral solution, as tolerated (not to exceed 60 milligrams per kilogram per day [mg/kg/day] for participants 2 to 15 years of age). The daily dosage was increased every 2 weeks by increments of 20 mg/kg/day to the recommended daily dosage of 60 mg/kg/day. The maximum recommended daily dosage was 3000 mg (1500 mg BID) for up to 1 year during open-label treatment phase. Participants were to either continue on commercially available levetiracetam or were tapered off of study drug over a period of up to 2 weeks during post-treatment phase of 30 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in BMD Z-score up to Month 12</title>
          <description>The BMD was measured by DEXA for the posterior-anterior lumbar spine (L1_L4) and total body less head area. The Z-Score is the number of standard deviations a participant's BMD differs from the average BMD of their age, sex and ethnicity. Positive scores indicate BMD above the mean; positive values are &quot;best values&quot; and negative values are &quot;worst values&quot;. Positive changes from baseline indicated an improvement in condition.</description>
          <population>The safety analysis set included all randomized participants who received at least 1 dose of study drug. Here 'N' (number of participants analyzed) signifies the number of participants evaluable for this outcome measure. Here, 'n' (number analyzed) signifies the number of participants evaluable at a specified category.</population>
          <units>Z-score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="24"/>
                <count group_id="O2" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Lumbar spine</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="23"/>
                    <count group_id="O2" value="30"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.346" spread="0.3461"/>
                    <measurement group_id="O2" value="0.084" spread="0.3552"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Total body less head</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="24"/>
                    <count group_id="O2" value="28"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.367" spread="0.3170"/>
                    <measurement group_id="O2" value="0.054" spread="0.3766"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Bone Mineral Content (BMC)-Z Score up to Month 6</title>
        <description>The BMC is an estimate of the amount of mineral (such as calcium) in the bone, which was assessed by DEXA scan for the posterior-anterior lumbar spine (L1_L4) and total body less head area. Positive changes from baseline indicated an improvement in condition.</description>
        <time_frame>Baseline up to Month 6</time_frame>
        <population>The safety analysis set included all randomized participants who received at least 1 dose of study drug. Here 'N' (number of participants analyzed) signifies the number of participants evaluable for this outcome measure. Here, 'n' (number analyzed) signifies the number of participants evaluable at a specified category.</population>
        <group_list>
          <group group_id="O1">
            <title>Topiramate</title>
            <description>Participants received topiramate weight-based sprinkle capsule and tablet, as tolerated (not to exceed 350 milligrams per day [mg/day] for participants 2 to less than [&lt;] 10 years of age, and not to exceed 400 mg/day for participants 10 to 15 years of age), twice daily (BID) for up to 1 year during open-label treatment phase. Participants were to either continue on commercially available topiramate or were tapered off of study drug over a period of up to 2 weeks during post-treatment phase of 30 days.</description>
          </group>
          <group group_id="O2">
            <title>Levetiracetam</title>
            <description>Participants received levetiracetam weight-based tablet or oral solution, as tolerated (not to exceed 60 milligrams per kilogram per day [mg/kg/day] for participants 2 to 15 years of age). The daily dosage was increased every 2 weeks by increments of 20 mg/kg/day to the recommended daily dosage of 60 mg/kg/day. The maximum recommended daily dosage was 3000 mg (1500 mg BID) for up to 1 year during open-label treatment phase. Participants were to either continue on commercially available levetiracetam or were tapered off of study drug over a period of up to 2 weeks during post-treatment phase of 30 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Bone Mineral Content (BMC)-Z Score up to Month 6</title>
          <description>The BMC is an estimate of the amount of mineral (such as calcium) in the bone, which was assessed by DEXA scan for the posterior-anterior lumbar spine (L1_L4) and total body less head area. Positive changes from baseline indicated an improvement in condition.</description>
          <population>The safety analysis set included all randomized participants who received at least 1 dose of study drug. Here 'N' (number of participants analyzed) signifies the number of participants evaluable for this outcome measure. Here, 'n' (number analyzed) signifies the number of participants evaluable at a specified category.</population>
          <units>Z-score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Lumbar spine</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="14"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.141" spread="0.2155"/>
                    <measurement group_id="O2" value="0.075" spread="0.2806"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Total body less head</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="15"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.242" spread="0.2516"/>
                    <measurement group_id="O2" value="0.151" spread="0.2154"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in BMC-Z Score up to Month 12</title>
        <description>The BMC is an estimate of the amount of mineral (such as calcium) in the bone, which was assessed by DEXA scan for the posterior-anterior lumbar spine (L1_L4) and total body less head area. Positive changes from baseline indicated an improvement in condition.</description>
        <time_frame>Baseline up to Month 12</time_frame>
        <population>The safety analysis set included all randomized participants who received at least 1 dose of study drug. Here 'N' (number of participants analyzed) signifies the number of participants evaluable for this outcome measure. Here, 'n' (number analyzed) signifies the number of participants evaluable at a specified category.</population>
        <group_list>
          <group group_id="O1">
            <title>Topiramate</title>
            <description>Participants received topiramate weight-based sprinkle capsule and tablet, as tolerated (not to exceed 350 milligrams per day [mg/day] for participants 2 to less than [&lt;] 10 years of age, and not to exceed 400 mg/day for participants 10 to 15 years of age), twice daily (BID) for up to 1 year during open-label treatment phase. Participants were to either continue on commercially available topiramate or were tapered off of study drug over a period of up to 2 weeks during post-treatment phase of 30 days.</description>
          </group>
          <group group_id="O2">
            <title>Levetiracetam</title>
            <description>Participants received levetiracetam weight-based tablet or oral solution, as tolerated (not to exceed 60 milligrams per kilogram per day [mg/kg/day] for participants 2 to 15 years of age). The daily dosage was increased every 2 weeks by increments of 20 mg/kg/day to the recommended daily dosage of 60 mg/kg/day. The maximum recommended daily dosage was 3000 mg (1500 mg BID) for up to 1 year during open-label treatment phase. Participants were to either continue on commercially available levetiracetam or were tapered off of study drug over a period of up to 2 weeks during post-treatment phase of 30 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in BMC-Z Score up to Month 12</title>
          <description>The BMC is an estimate of the amount of mineral (such as calcium) in the bone, which was assessed by DEXA scan for the posterior-anterior lumbar spine (L1_L4) and total body less head area. Positive changes from baseline indicated an improvement in condition.</description>
          <population>The safety analysis set included all randomized participants who received at least 1 dose of study drug. Here 'N' (number of participants analyzed) signifies the number of participants evaluable for this outcome measure. Here, 'n' (number analyzed) signifies the number of participants evaluable at a specified category.</population>
          <units>Z-score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Lumbar spine</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="14"/>
                    <count group_id="O2" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.274" spread="0.3123"/>
                    <measurement group_id="O2" value="0.124" spread="0.3584"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Total body less head</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="15"/>
                    <count group_id="O2" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.266" spread="0.6800"/>
                    <measurement group_id="O2" value="0.017" spread="0.2533"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Treatment-emergent Adverse Events (TEAE)</title>
        <description>An adverse event (AE) is any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. TEAE are defined as AEs with onset during the treatment period or that are a consequence of a pre-existing condition that has worsened since baseline.</description>
        <time_frame>Up to Day 390</time_frame>
        <population>Safety analysis set included all randomized participants who received at least 1 dose of study treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>Topiramate</title>
            <description>Participants received topiramate weight-based sprinkle capsule and tablet, as tolerated (not to exceed 350 milligrams per day [mg/day] for participants 2 to less than [&lt;] 10 years of age, and not to exceed 400 mg/day for participants 10 to 15 years of age), twice daily (BID) for up to 1 year during open-label treatment phase. Participants were to either continue on commercially available topiramate or were tapered off of study drug over a period of up to 2 weeks during post-treatment phase of 30 days.</description>
          </group>
          <group group_id="O2">
            <title>Levetiracetam</title>
            <description>Participants received levetiracetam weight-based tablet or oral solution, as tolerated (not to exceed 60 milligrams per kilogram per day [mg/kg/day] for participants 2 to 15 years of age). The daily dosage was increased every 2 weeks by increments of 20 mg/kg/day to the recommended daily dosage of 60 mg/kg/day. The maximum recommended daily dosage was 3000 mg (1500 mg BID) for up to 1 year during open-label treatment phase. Participants were to either continue on commercially available levetiracetam or were tapered off of study drug over a period of up to 2 weeks during post-treatment phase of 30 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Treatment-emergent Adverse Events (TEAE)</title>
          <description>An adverse event (AE) is any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. TEAE are defined as AEs with onset during the treatment period or that are a consequence of a pre-existing condition that has worsened since baseline.</description>
          <population>Safety analysis set included all randomized participants who received at least 1 dose of study treatment.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="28"/>
                <count group_id="O2" value="35"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25"/>
                    <measurement group_id="O2" value="29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Kidney Stones</title>
        <description>Percentage of participants with kidney stones were reported.</description>
        <time_frame>Up to Day 390</time_frame>
        <population>Safety analysis set included all randomized subjects who received at least 1 dose of study treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>Topiramate</title>
            <description>Participants received topiramate weight-based sprinkle capsule and tablet, as tolerated (not to exceed 350 milligrams per day [mg/day] for participants 2 to less than [&lt;] 10 years of age, and not to exceed 400 mg/day for participants 10 to 15 years of age), twice daily (BID) for up to 1 year during open-label treatment phase. Participants were to either continue on commercially available topiramate or were tapered off of study drug over a period of up to 2 weeks during post-treatment phase of 30 days.</description>
          </group>
          <group group_id="O2">
            <title>Levetiracetam</title>
            <description>Participants received levetiracetam weight-based tablet or oral solution, as tolerated (not to exceed 60 milligrams per kilogram per day [mg/kg/day] for participants 2 to 15 years of age). The daily dosage was increased every 2 weeks by increments of 20 mg/kg/day to the recommended daily dosage of 60 mg/kg/day. The maximum recommended daily dosage was 3000 mg (1500 mg BID) for up to 1 year during open-label treatment phase. Participants were to either continue on commercially available levetiracetam or were tapered off of study drug over a period of up to 2 weeks during post-treatment phase of 30 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Kidney Stones</title>
          <description>Percentage of participants with kidney stones were reported.</description>
          <population>Safety analysis set included all randomized subjects who received at least 1 dose of study treatment.</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="28"/>
                <count group_id="O2" value="35"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Up to Day 390</time_frame>
      <desc>The safety analysis set included all randomized participants who received at least 1 dose of study drug.</desc>
      <group_list>
        <group group_id="E1">
          <title>Topiramate</title>
          <description>Participants received topiramate weight-based sprinkle capsule and tablet, as tolerated (not to exceed 350 milligrams per day [mg/day] for participants 2 to less than [&lt;] 10 years of age, and not to exceed 400 mg/day for participants 10 to 15 years of age), twice daily (BID) for up to 1 year during open-label treatment phase. Participants were to either continue on commercially available topiramate or were tapered off of study drug over a period of up to 2 weeks during post-treatment phase of 30 days.</description>
        </group>
        <group group_id="E2">
          <title>Levetiracetam</title>
          <description>Participants received levetiracetam weight-based tablet or oral solution, as tolerated (not to exceed 60 milligrams per kilogram per day [mg/kg/day] for participants 2 to 15 years of age). The daily dosage was increased every 2 weeks by increments of 20 mg/kg/day to the recommended daily dosage of 60 mg/kg/day. The maximum recommended daily dosage was 3000 mg (1500 mg BID) for up to 1 year during open-label treatment phase. Participants were to either continue on commercially available levetiracetam or were tapered off of study drug over a period of up to 2 weeks during post-treatment phase of 30 days.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA Version 22.1</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="35"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Skull Fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="35"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Myositis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="35"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Epilepsy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Generalised Tonic-Clonic Seizure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Seizure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="35"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>2</frequency_threshold>
        <default_vocab>MedDRA Version 22.1</default_vocab>
        <default_assessment>Non-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="25" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="29" subjects_at_risk="35"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Eosinophilia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="35"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Palpitations</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="35"/>
              </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="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Middle Ear Effusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Vertigo</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="35"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal Pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Abdominal Pain Upper</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Epigastric Discomfort</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Paraesthesia Oral</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="35"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Influenza Like Illness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Sluggishness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="35"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Conjunctivitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Ear Infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Gastroenteritis Enteroviral</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Gastrointestinal Infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Impetigo</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Laryngitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Pharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Pneumococcal Infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Pulpitis Dental</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Respiratory Tract Infection Viral</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Rhinitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Scarlet Fever</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Staphylococcal Infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Staphylococcal Pharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Systemic Viral Infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Tonsillitis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Upper Respiratory Tract Infection</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Varicella</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Viral Infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="35"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Concussion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Head Injury</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Lip Injury</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Thermal Burn</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Tooth Fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="35"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Ammonia Decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Blood Potassium Increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Blood Triglycerides Increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Platelet Count Decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Vitamin D Decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Weight Decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="35"/>
              </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="4" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Metabolic Acidosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="35"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="35"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Skin Papilloma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="35"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Ataxia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Balance Disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Cognitive Disorder</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Disturbance in Attention</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Dizziness Exertional</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Hypoaesthesia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Memory Impairment</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Mental Impairment</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Partial Seizures</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Psychomotor Hyperactivity</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="35"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Affective Disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Agitation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Attention Deficit/Hyperactivity Disorder</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Emotional Disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Hyposomnia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Irritability</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Learning Disorder</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Mood Swings</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Nervousness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Sleep Disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="35"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Nephrolithiasis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="35"/>
              </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="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="35"/>
              </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="1" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Oropharyngeal Pain</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Rhinitis Allergic</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Rhinorrhoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Throat Tightness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="35"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Blister</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Dermatitis Allergic</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Eczema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Keratosis Pilaris</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Rash Papular</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Rash Pruritic</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="35"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Flushing</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="35"/>
              </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>If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days.</restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>Due to futility of enrollment, the enrollment was stopped early; however, all enrolled participants completed the full course of the trial excluding 7 participants (reasons captured in &quot;participant flow&quot;). Also, there was no exposure to topiramate in 2 to 5 years age cohort. Therefore, no conclusions can be made with regard to this age group due to the absence of comparability.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Director - Clinical Leader</name_or_title>
      <organization>Janssen Research &amp; Development, LLC</organization>
      <phone>844-434-4210</phone>
      <email>ClinicalTrialDisclosure@its.jnj.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/NCT02201251
org study id: CR104425
secondary id: TOPMATEPY4067
secondary id: 2012-001552-19
nct id: NCT02201251
lead sponsor: 
has dmc: Yes
is fda regulated device: No
The purpose of this study is to evaluate the safety of topiramate monotherapy compared with
      levetiracetam another standard antiepileptic drug (AED), as monotherapy for new-onset or
      recent-onset epilepsy (seizure disorder) on pediatric growth and maturation, bone
      mineralization, and kidney stone formation in children aged 2 to 15 years.
This is a randomized (study medication assigned to participants by chance), open-label,
      multi-centric (conducted in more than one center) and 2-arm flexible-dose monotherapy study
      of topiramate compared with 1 another AED (levetiracetam) in pediatric participants with
      epilepsy. The total study duration will be up to of 1 year and 2 months per participant. The
      study consists of 3 parts: Screening (that is, up to 35 days before study commences on Day
      1); Treatment (1 year) and post-treatment (30 days). Safety will primarily be evaluated by
      percentage of participants with kidney stones and change from baseline in bone mineral
      density at Month 12.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Health Services Research
masking: None (Open Label)
measure: Change From Baseline in Weight Z-score up to Month 1
time frame: Baseline up to Month 1
description: The Z-Score indicates how many standard deviations (SD) a participant has from the population normal values. The body weight z-scores were designed to take into account the amount of weight gain that was expected due to normal growth in children and adolescents. Body weight data were converted to Z-scores using the Statistical Analysis System (SAS) programs provided by the Centers for Disease Control (CDC) for the calculation of the 2000 CDC growth charts. The mean (SD) change in Z scores from baseline up to Month 1 for the total safety population for all age cohorts combined were presented. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.
measure: Change From Baseline in Weight Z-score up to Month 3
time frame: Baseline up to Month 3
description: The Z-Score indicates how many SD a participant has from the population normal values. The body weight z-scores were designed to take into account the amount of weight gain that was expected due to normal growth in children and adolescents. Body weight data were converted to Z-scores using the SAS programs provided by the CDC for the calculation of the 2000 CDC growth charts. The mean (SD) change in Z scores from baseline up to Month 3 for the total safety population for all age cohorts combined were presented. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.
measure: Change From Baseline in Weight Z-score up to Month 6
time frame: Baseline up to Month 6
description: The Z-Score indicates how many SD a participant has from the population normal values. The body weight z-scores were designed to take into account the amount of weight gain that was expected due to normal growth in children and adolescents. Body weight data were converted to Z-scores using the SAS programs provided by the CDC for the calculation of the 2000 CDC growth charts. The mean (SD) change in Z scores from baseline up to Month 6 for the total safety population for all age cohorts combined were presented. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.
measure: Change From Baseline in Weight Z-score up to Month 9
time frame: Baseline up to Month 9
description: The Z-Score indicates how many SD a participant has from the population normal values. The body weight z-scores were designed to take into account the amount of weight gain that was expected due to normal growth in children and adolescents. Body weight data were converted to Z-scores using the SAS programs provided by the CDC for the calculation of the 2000 CDC growth charts. The mean (SD) change in Z scores from baseline up yo Month 9 for the total safety population for all age cohorts combined were presented. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.
measure: Change From Baseline in Weight Z-score up to Month 12
time frame: Baseline up to Month 12
description: The Z-Score indicates how many SD a participant has from the population normal values. The body weight z-scores were designed to take into account the amount of weight gain that was expected due to normal growth in children and adolescents. Body weight data were converted to Z-scores using the SAS programs provided by the CDC for the calculation of the 2000 CDC growth charts. The mean (SD) change in Z scores from baseline to Month 12 for the total safety population for all age cohorts combined were presented. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.
measure: Change From Baseline in Height Z-score up to Month 1
time frame: Baseline up to Month 1
description: Z-Score was a statistical measure to evaluate how a single data point compares to a standard. It described whether a mean was above or below the standard and how unusual the measurement is with range from minus (-) 3 to plus (+) 3; 0 equal to (=) same mean, greater than (>) 0 a greater mean, and less than (<) 0 a lesser mean than the standard. Growth parameters were compared to a standard defined by CDC growth charts. The mean (SD) change in Z scores from baseline up to Month 1 for the total safety population for all age cohorts combined were presented. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.
measure: Change From Baseline in Height Z-score up to Month 3
time frame: Baseline up to Month 3
description: Z-Score was a statistical measure to evaluate how a single data point compares to a standard. It described whether a mean was above or below the standard and how unusual the measurement is with range from -3 to +3; 0 =same mean, >0 a greater mean, and <0 a lesser mean than the standard. Growth parameters were compared to a standard defined by CDC growth charts. The mean (SD) change in Z scores from baseline up to Month 3 for the total safety population for all age cohorts combined were presented. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.
measure: Change From Baseline in Height Z-score up to Month 6
time frame: Baseline up to Month 6
description: Z-Score was a statistical measure to evaluate how a single data point compares to a standard. It described whether a mean was above or below the standard and how unusual the measurement is with range from -3 to +3; 0 =same mean, >0 a greater mean, and <0 a lesser mean than the standard. Growth parameters were compared to a standard defined by CDC growth charts. The mean (SD) change in Z scores from baseline up to Month 6 for the total safety population for all age cohorts combined were presented.
measure: Change From Baseline in Height Z-score up to Month 9
time frame: Baseline up to Month 9
description: Z-Score was a statistical measure to evaluate how a single data point compares to a standard. It described whether a mean was above or below the standard and how unusual the measurement is with range from -3 to +3; 0 =same mean, >0 a greater mean, and <0 a lesser mean than the standard. Growth parameters were compared to a standard defined by CDC growth charts. The mean (SD) change in Z scores from baseline up to Month 9 for the total safety population for all age cohorts combined were presented. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.
measure: Change From Baseline in Height Z-score up to Month 12
time frame: Baseline up to Month 12
description: Z-Score was a statistical measure to evaluate how a single data point compares to a standard. It described whether a mean was above or below the standard and how unusual the measurement is with range from -3 to +3; 0 =same mean, >0 a greater mean, and <0 a lesser mean than the standard. Growth parameters were compared to a standard defined by CDC growth charts. The mean (SD) change in Z scores from baseline up to Month 12 for the total safety population for all age cohorts combined were presented. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.
measure: Change From Baseline in Bone Mineral Density (BMD) Z-score up to Month 6
time frame: Baseline up to Month 6
description: The BMD was measured by dual energy X-ray absorptiometry (DEXA) for the posterior-anterior lumbar spine (L1_L4) and total body less head area. The Z-Score is the number of standard deviations a participant's BMD differs from the average BMD of their age, sex and ethnicity. Positive scores indicate BMD above the mean; positive values are "best values" and negative values are "worst values". Positive changes from baseline indicated an improvement in condition.
measure: Change From Baseline in BMD Z-score up to Month 12
time frame: Baseline up to Month 12
description: The BMD was measured by DEXA for the posterior-anterior lumbar spine (L1_L4) and total body less head area. The Z-Score is the number of standard deviations a participant's BMD differs from the average BMD of their age, sex and ethnicity. Positive scores indicate BMD above the mean; positive values are "best values" and negative values are "worst values". Positive changes from baseline indicated an improvement in condition.
measure: Change From Baseline in Bone Mineral Content (BMC)-Z Score up to Month 6
time frame: Baseline up to Month 6
description: The BMC is an estimate of the amount of mineral (such as calcium) in the bone, which was assessed by DEXA scan for the posterior-anterior lumbar spine (L1_L4) and total body less head area. Positive changes from baseline indicated an improvement in condition.
measure: Change From Baseline in BMC-Z Score up to Month 12
time frame: Baseline up to Month 12
description: The BMC is an estimate of the amount of mineral (such as calcium) in the bone, which was assessed by DEXA scan for the posterior-anterior lumbar spine (L1_L4) and total body less head area. Positive changes from baseline indicated an improvement in condition.
measure: Number of Participants With Treatment-emergent Adverse Events (TEAE)
time frame: Up to Day 390
description: An adverse event (AE) is any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. TEAE are defined as AEs with onset during the treatment period or that are a consequence of a pre-existing condition that has worsened since baseline.
measure: Percentage of Participants With Kidney Stones
time frame: Up to Day 390
description: Percentage of participants with kidney stones were reported.
arm group label: Topiramate
arm group type: Experimental
description: Topiramate weight based dosing for participants 2 to less than (<) 10 years of age not to exceed 350 mg/day (milligram per day), as tolerated; not to exceed 400 mg/day in participants 10-15 years of age, as tolerated.
arm group label: Levetiracetam
arm group type: Active Comparator
description: Levetiracetam weight based dosing for all participants 2-15 years of age, not to exceed 60 milligram per kilogram per day (mg/kg/day), as tolerated. The maximum recommended daily dosage is 3,000 milligram (mg).
intervention type: Drug
intervention name: Topiramate
description: Topiramate weight based dosing for participants 2 to <10 years of age not to exceed 350 mg/day, as tolerated; not to exceed 400 mg/day in participants 10-15 years of age, as tolerated.
arm group label: Topiramate
intervention type: Drug
intervention name: Levetiracetam
description: Levetiracetam weight based dosing for all participants 2-15 years of age, not to exceed 60 mg/kg/day, as tolerated. The maximum recommended daily dosage is 3,000 mg.
arm group label: Levetiracetam
criteria: 
gender: All
minimum age: 2 Years
maximum age: 15 Years
healthy volunteers: No
last name: Janssen Research & Development, LLC Clinical Trial
role: Study Director
affiliation: Janssen Research & Development, LLC
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country: Argentina
country: Australia
country: Austria
country: Belgium
country: Canada
country: France
country: Germany
country: Hungary
country: Philippines
country: Poland
country: Russian Federation
country: South Africa
country: Taiwan
country: United States
country: China
country: Italy
country: Korea, Republic of
country: Mexico
country: Spain
country: Thailand
country: United Kingdom
responsible party type: Sponsor
mesh term: Epilepsy
mesh term: Topiramate
mesh term: Levetiracetam
provided document: 
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participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Due to futility of enrollment, the enrollment was stopped early; however, all enrolled participants completed the full course of the trial excluding 7 participants (reasons captured in "participant flow"). Also, there was no exposure to topiramate in 2 to 5 years age cohort. Therefore, no conclusions can be made with regard to this age group due to the absence of comparability.
point of contact: 