<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/NCT02201108</url>
  </required_header>
  <id_info>
    <org_study_id>EFC11759</org_study_id>
    <secondary_id>2011-005249-12</secondary_id>
    <secondary_id>U1111-1124-0983</secondary_id>
    <nct_id>NCT02201108</nct_id>
  </id_info>
  <brief_title>Efficacy, Safety and Pharmacokinetics of Teriflunomide in Pediatric Patients With Relapsing Forms of Multiple Sclerosis</brief_title>
  <acronym>TERIKIDS</acronym>
  <official_title>A Two Year, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Trial to Evaluate Efficacy, Safety, Tolerability, and Pharmacokinetics of Teriflunomide Administered Orally Once Daily in Pediatric Patients With Relapsing Forms of Multiple Sclerosis Followed by an Open-Label Extension</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Genzyme, a Sanofi Company</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sanofi</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Primary Objective:&#xD;
&#xD;
      To assess the effect of teriflunomide in comparison to placebo on disease activity measured&#xD;
      by time to first clinical relapse after randomization in children and adolescents 10 to 17&#xD;
      years of age with relapsing forms of multiple sclerosis (MS).&#xD;
&#xD;
      Secondary Objective:&#xD;
&#xD;
        -  To assess the effect of teriflunomide in comparison to placebo on disease&#xD;
           activity/progression measured by brain magnetic resonance imaging (MRI) and on cognitive&#xD;
           function.&#xD;
&#xD;
        -  To evaluate the safety and tolerability of teriflunomide in comparison to placebo.&#xD;
&#xD;
        -  To evaluate the pharmacokinetics (PK) of teriflunomide.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study duration included a screening period up to 4 weeks, a double-blind treatment period&#xD;
      of up to 96 weeks, an open-label period which included the remainder of the initial 96 weeks,&#xD;
      where applicable, and a 96-week extension, i.e., up to a maximum of 192 weeks after&#xD;
      randomization. There was a follow-up period of 4 weeks for participants discontinuing&#xD;
      treatment.&#xD;
&#xD;
      Within the 96 weeks double-blind treatment period, the first 4 weeks were PK run-in phase in&#xD;
      which PK samples (blood samples) were collected from participants and then 4 weeks of&#xD;
      analysis (no samples drawn). The PK run-in phase (total 8 weeks) was intended to provide&#xD;
      individual PK parameters to allow the dose adjustment to the 14 milligrams (mg)&#xD;
      adult-equivalent dose for the rest of the study.&#xD;
&#xD;
      Participants who experienced a relapse after the PK run-in phase (8 weeks) and confirmed by&#xD;
      the Relapse Adjudication Panel and participants who fulfilled MRI criteria (high number of&#xD;
      new lesions at weeks 36, 48 or 72 compared to previous images) had the option to continue in&#xD;
      an open-label teriflunomide treatment arm up to 192 weeks from randomization.&#xD;
&#xD;
      An optional additional extension period is available for young participants with&#xD;
      teriflunomide until the participants are 18 years old and/or able to switch to commercial&#xD;
      product, whichever comes first.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">July 16, 2014</start_date>
  <completion_date type="Anticipated">June 25, 2025</completion_date>
  <primary_completion_date type="Actual">October 25, 2019</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>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Time to First Confirmed Clinical Relapse</measure>
    <time_frame>Baseline up to Week 96</time_frame>
    <description>Time to first clinical relapse was defined as the duration (in weeks) between randomization and first confirmed clinical relapse. Clinical relapses were defined as new or recurrent neurological symptoms not associated with fever or infection, lasting at least 24 hours, and accompanied by new objective neurological findings upon neurological examination and documented by a standardized, quantified functional system score (FSSs) which included 8 items and items were rated on different scales: brain stem, cerebellar and cerebral functions rated on a scale of 0 to 5; visual, pyramidal, sensory and bowel/bladder rated on a scale of 0 to 6 and ambulation on a scale of 0 to 12, where higher score in each scale indicated worsened neurological function. Confirmed clinical relapse were reviewed and confirmed by an independent Relapse Adjudication Panel (RAP). A participant without confirmed clinical relapse, was considered as clinical relapse free until the end of Week 96.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Probability of Participants Who Were Clinical Relapse Free at Weeks 24, 48, 72, 96, 120, 144, 168 and 192</measure>
    <time_frame>Weeks 24, 48, 72, 96, 120, 144, 168 and 192</time_frame>
    <description>Participant was considered free of clinical relapse if the participant had no confirmed clinical relapse before treatment discontinuation/completion in 192 weeks treatment period. Clinical relapses: new/recurrent neurological symptoms not associated with fever/infection, lasted at least 24 hours, and accompanied by new objective neurological findings upon neurological examination and documented by standardized, quantified FSSs which included 8 items: rated on different scales: brain stem, cerebellar and cerebral functions rated on scale of 0 to 5; visual, pyramidal, sensory and bowel/bladder rated on scale of 0 to 6 &amp; ambulation on scale of 0 to 12, where higher score in each scale indicated worsened neurological function. New/recurrent symptoms occurred less than 30 days following onset of relapse were considered part of same relapse. Probability of participants who were clinical relapse free at specified weeks were estimated by Kaplan-Meier method and reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Brain Magnetic Resonance Imaging (MRI) Assessment: Number of New or Enlarged T2 Lesions Per MRI Scan</measure>
    <time_frame>Baseline up to Week 192</time_frame>
    <description>Number of new or enlarged T2 lesions per scan was defined as the total number of new or enlarged T2 lesion that occurred during the 192 weeks treatment period divided by the total number of scans performed during 192 weeks. To account for the different numbers of scans performed among the participants, a negative binomial regression model with robust variance estimation was used. The model included the total number of new or enlarged T2-lesions as the response variable, with treatment group, region, pubertal status and age as covariates and log-transformed number of scans as an offset variable.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Brain Magnetic Resonance Imaging Assessment: Number of T1 Gadolinium (Gd)-Enhancing T1 Lesions Per MRI Scan</measure>
    <time_frame>Baseline up to Week 192</time_frame>
    <description>The number of T1 Gd-Enhancing lesions per scan was defined as the total number of Gd-enhancing lesions that occurred during the 192 weeks treatment period divided by the total number of scans performed during 192 weeks. To account for the different number of scans performed among the participants, a negative binomial regression model with robust variance estimation was used. The model included the total number of T1-lesions as the response variable, with treatment group, region, pubertal status and age as covariates and log-transformed number of scans as an offset variable.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Brain Magnetic Resonance Imaging Assessment: Change From Baseline in Volume of T2 Lesions at Weeks 24, 36, 48, 72, 96, 144 and 192</measure>
    <time_frame>Baseline, DB period: Weeks 24, 36, 48, 72 and 96; OL period: Weeks 48, 96, 144 and 192</time_frame>
    <description>Volume of T2 lesions was measured by MRI scan.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Brain Magnetic Resonance Imaging Assessment: Change From Baseline in Volume of T1 Hypointense Lesions</measure>
    <time_frame>Baseline, DB period: Weeks 24, 36, 48, 72 and 96; OL period: Weeks 48, 96, 144 and 192</time_frame>
    <description>Volume of T1 hypointense lesions was measured by MRI scan.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Brain Magnetic Resonance Imaging Assessment: Number of New T1 Hypointense Lesions Per MRI Scan</measure>
    <time_frame>Baseline up to Week 192</time_frame>
    <description>The number of new T1 hypointense lesions were obtained from MRI scans.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Brain Magnetic Resonance Imaging Assessment: Percentage of Participants Free of New or Enlarged MRI T2-Lesions</measure>
    <time_frame>Baseline, Weeks 24, 48, 72, 96, 144 and 192</time_frame>
    <description>Percentage of participants who were free of new or enlarged T2 lesions at Weeks 24, 48, 72, 96, 144 and 192 were reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Brain Magnetic Resonance Imaging Assessment: Percent Change From Baseline in Brain Volume at Weeks 24, 36, 48, 72, 96, 144 and 192</measure>
    <time_frame>Baseline, DB period: Weeks 24, 36, 48, 72 and 96; OL period: Weeks 48, 96, 144 and 192</time_frame>
    <description>Percent change from baseline in brain volume (assessed using MRI scans of the Brain) at Weeks 24, 36, 48,72, 96, 144 and 192 was reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cognitive Assessment: Change From Baseline in Total Number of Correct Substitutions Measured by Symbol Digit Modalities Test (SDMT) at Weeks 24, 48, 72, 96, 120, 144, 168 and 192</measure>
    <time_frame>Baseline, DB period: Weeks 24, 48, 72 and 96; OL period: Weeks 24, 48, 72, 96, 120, 144, 168 and 192</time_frame>
    <description>SDMT measures the time to pair abstract symbols with specific numbers. It is a simple substitution task that gives the examinee 90 seconds to pair specific numbers with given geometric figures as a measure for screening cognitive impairment. The SDMT score is the number of correct substitution and ranged from 0 (worst outcome) to 110 (best outcome), where higher score indicated better cognitive function.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cognitive Assessment: Change From Baseline in Number of Completed Items Measured by Symbol Digit Modalities Test at Weeks 24, 48, 72, 96, 120, 144, 168 and 192</measure>
    <time_frame>Baseline, DB period: Weeks 24, 48, 72 and 96; OL period: Weeks 24, 48, 72, 96, 120, 144, 168 and 192</time_frame>
    <description>SDMT measures the time to pair abstract symbols with specific numbers. It is a simple substitution task that gives the examinee 90 seconds to pair specific numbers with given geometric figures as a measure for screening cognitive impairment. The SDMT score is the number of completed items and ranged from 0 (worst outcome) to 110 (best outcome), where higher score indicated better cognitive function.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cognitive Assessment: Change From Baseline in Brief Visuospatial Memory Test-Revised (BVMT-R) Scores at Weeks 96 and 192</measure>
    <time_frame>Baseline, Weeks 96 and 192</time_frame>
    <description>The BVMT consists of three trials in which participants must recall shapes by drawing figures on a blank page (response booklet) after being given the opportunity to memorize the figures (given in BMVT-R form) for 10 seconds. BMVT-R form consists of six figures. Points are awarded based on the accuracy of the drawn figure and by correct placement on the blank page. A minimum of 0 to 12 points/scores are awarded per trial, so a participant can score between 0 and 36 points for all three trials (by adding the points/score from each trial), where higher score indicates better outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cognitive Assessment: Change From Baseline in Trail Making Test- Part A (TMT-A) Test Scores (in Seconds) at Week 96 and 192</measure>
    <time_frame>Baseline, Weeks 96 and 192</time_frame>
    <description>'Trail Making Test Part A' is a neuropsychological test of visual attention and task switching. The task requires a participant to 'connect-the-dots' of 25 consecutive numbers (1,2, 3, etc.) in sequential order on a sheet of paper or computer screen. The goal of the participant is to finish the test as quickly as possible, and the time taken to complete the test used as the primary performance metric (in seconds). This is a timed test and the number of seconds to complete the task is recorded. Maximum time allowed is 300 seconds. A lower score indicated better cognitive function.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cognitive Assessment: Change From Baseline in Trail Making Test B (TMT-B) Test Scores (in Seconds) at Weeks 96 and 192</measure>
    <time_frame>Baseline, Weeks 96 and 192</time_frame>
    <description>TMT-B is a cognitive test that gives a measure of various aspects of cognitive performance. It is used to measure cognitive fatigue. The test consisted of 25 circles containing 13 sequential numbers (1 to 13) and 12 sequential letters (A to L) positioned. The test evaluates the time (in seconds) to correctly order letters and numbers in alternate order (1, A, 2, B etc.). Maximum time allowed is 300 seconds, where less time/lower score indicated better cognitive function/performance.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cognitive Assessment: Change From Baseline in Beery Visual-motor Integration (BVMI) Scores at Weeks 96 and 192</measure>
    <time_frame>Baseline, Weeks 96 and 192</time_frame>
    <description>The Beery VMI is a non-verbal assessment that assessed the extent to which individuals can integrate their visual and motor abilities. The participants were provided with geometric designs ranging from simple line drawings to more complex figures and were asked to copy the designs. The test consisted of 24 figures. One point was scored for each successful copy of drawings and no scoring was given when the participant failed to copy the drawings properly. Each successful copying of drawings was summed up and the total was scored on a scale ranged from 0 to 24, where higher score indicated better visual construction skills/better visual and motor abilities and lower score indicated poor visual construction skills/poor visual and motor abilities.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cognitive Assessment: Change From Baseline in Wechsler Abbreviated Scale of Intelligence-II (WASI-II) Vocabulary Total Raw Scores at Weeks 96 and 192</measure>
    <time_frame>Baseline, Weeks 96 and 192</time_frame>
    <description>The WASI-II: Vocabulary test is a quick estimate of an individual's level of intellectual functioning which comprised of 31 total items that required the participant to orally define 3 images and 28 words presented both orally and visually. Items 1 to 3 rated on a score of 0 or 1, items 4 and 5 rated on a score of 0 or 2, items 6 to 31 rated on a scale of 0 to 2. Each item score was summed up to derive the total score which ranged from 0 (minimum score) to 59 (maximum score), where higher score indicated better level of intellectual functioning/higher level of intelligence.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cognitive Assessment: Change From Baseline in Delis-Kaplan Executive Function System (D-KEFS) Letter Fluency Total Correct Raw Score at Weeks 96 and 192</measure>
    <time_frame>Baseline, Weeks 96 and 192</time_frame>
    <description>Letter Fluency is a condition measured in the D-KEFS. Participants were asked to name as many words as they can, starting with a specified letter for 60 seconds. The words cannot be names, places, numbers or grammatical variants of previous answers. Repeated answers were not scored as a correct response. There were 3 trials, with 3 different letters. The total number of correct responses was totaled for all 3 trials and a letter fluency score was given. A higher score was considered better. There was no set range as the score depends on how many correct words the participant relays in the given time period.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cognitive Assessment: Change From Baseline in Delis-Kaplan Executive Function System Category Fluency Total Correct Raw Score at Weeks 96 and 192</measure>
    <time_frame>Baseline, Weeks 96 and 192</time_frame>
    <description>Category Fluency is a condition measured in the D-KEFS. It measured participant's ability to generate words from three different categories (e.g., fruits, vegetables and animals), within a minute for each category. Total score was number of correct words for each category with no points for repetitions or non-words. Score ranged from 0 to unlimited, where 0 = low score, higher score indicated better performance.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cognitive Assessment - Selective Reminding Test (SRT): Change From Baseline in Total Number of Words on Delayed Recall at Weeks 96 and 192</measure>
    <time_frame>Baseline, Weeks 96 and 192</time_frame>
    <description>SRT is a test to assess verbal learning and memory. During the administration of the SRT only the examiner and the participant should be in the testing room. A list of twelve words was read aloud by the examiner at a rate of one word per two seconds. The participant is asked to recall all twelve words after a 30 minute delay. Only the words that were missed on the preceding trial were given in the consecutive trial. The total score represented a sum score of total 6 trials, therefore the score range was from 0 to 72. The lower the score the worse the outcome, higher score indicated better recall.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DB: Pharmacokinetics: Steady-state Trough Concentration (Ctrough) of Teriflunomide</measure>
    <time_frame>Predose on Week 36</time_frame>
    <description>Ctrough was defined as the concentration reached by the drug before the next dose administered. Data for this outcome measure was planned to be collected and analyzed separately for each dose of Teriflunomide. PK samples for teriflunomide 3.5 mg were collected during the first 8 weeks but all participants were switched to teriflunomide 7 mg after Week 8. Hence, plasma concentration of teriflunomide 7 mg and 14 mg were reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>OL: Time to First Confirmed Clinical Relapse</measure>
    <time_frame>Baseline up to Week 192</time_frame>
    <description>Time to first clinical relapse was defined as duration (in weeks) after enrollment in OL period and first confirmed clinical relapse. Clinical relapses were defined as new or recurrent neurological symptoms not associated with fever or infection, lasted at least 24 hours and accompanied by new objective neurological findings upon neurological examination and documented by standardized, quantified FSSs which included 8 items and items were rated on different scales: brain stem, cerebellar &amp; cerebral functions rated on scale of 0 to 5; visual, pyramidal, sensory and bowel/bladder rated on scale of 0 to 6 and ambulation on scale of 0 to 12 where higher score in each scale indicated worsened neurological function. Confirmed clinical relapse were reviewed and confirmed by independent RAP. Participant without confirmed clinical relapse, was considered as clinical relapse free until end of Week 192.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>OL: Pharmacokinetics: Steady-state Trough Concentration (Ctrough) of Teriflunomide</measure>
    <time_frame>Pre-dose at Week 36</time_frame>
    <description>Ctrough was defined as the concentration reached by the drug before the next dose is administered. Data for this outcome measure was planned to be collected and analyzed separately for each dose of teriflunomide. PK samples for teriflunomide 3.5 mg were collected during the first 8 weeks but all participants were switched to teriflunomide 7 mg after Week 8. Hence, plasma concentration of teriflunomide 7 mg and 14 mg were reported.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">166</enrollment>
  <condition>Multiple Sclerosis</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Matching placebo tablets</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Teriflunomide</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Teriflunomide oral tablet, three dosages (3.5, 7 or 14 mg) to reach 14 mg adult equivalent</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Teriflunomide</intervention_name>
    <description>Pharmaceutical form:film-coated tablet, Route of administration: oral</description>
    <arm_group_label>Teriflunomide</arm_group_label>
    <other_name>AUBAGIO, HMR1726</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Pharmaceutical form:tablet, Route of administration: oral</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        -  Participants with relapsing MS were eligible. Participants who met the criteria of MS&#xD;
             based on McDonald criteria 2010 and International Pediatric Multiple Sclerosis Study&#xD;
             Group (IPMSSG) criteria for pediatric MS, version of 2012 and had:&#xD;
&#xD;
               -  at least one relapse (or attack) in the 12 months preceding screening or,&#xD;
&#xD;
               -  at least two relapses (or attack) in the 24 months preceding screening.&#xD;
&#xD;
          -  Less than 18 years of age and greater than or equal to (&gt;=) 10 years of age at&#xD;
             randomization. Specific for the Russian Federation from 18 December 2014 to 26 July&#xD;
             2016, less than or equal to 17 years of age and &gt;= 13 years of age at randomization.&#xD;
&#xD;
          -  Signed informed consent/assent obtained from participant and participant's legal&#xD;
             representative (parents or guardians) according to local regulations.&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  Expanded disability status scale score greater than 5.5 at screening or randomization&#xD;
             visits.&#xD;
&#xD;
          -  Relapse within 30 days prior to randomization.&#xD;
&#xD;
          -  Treated with:&#xD;
&#xD;
               -  glatiramer acetate, interferons, or dimethyl fumarate within 1 month prior to&#xD;
                  randomization.&#xD;
&#xD;
               -  fingolimod, or intravenous immunoglobulins within 3 months prior to&#xD;
                  randomization.&#xD;
&#xD;
               -  natalizumab, other immunosuppressant or immunomodulatory agents such as&#xD;
                  cyclophosphamide, azathioprine, cyclosporine, methotrexate, mycophenolate, within&#xD;
                  6 months prior to randomization.&#xD;
&#xD;
               -  cladribine or mitoxantrone within 2 years prior to randomization.&#xD;
&#xD;
          -  Treated with alemtuzumab at any time.&#xD;
&#xD;
          -  History of human immunodeficiency virus infection.&#xD;
&#xD;
          -  Contraindication for MRI.&#xD;
&#xD;
          -  Pregnant or breast-feeding females or those who plan to become pregnant during the&#xD;
             study.&#xD;
&#xD;
          -  Female participants of child-bearing potential not using highly effective&#xD;
             contraceptive method (contraception in both female and male was required).&#xD;
&#xD;
        The above information was not intended to contain all considerations relevant to a&#xD;
        participant's potential participation in a clinical trial.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>10 Years</minimum_age>
    <maximum_age>17 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Clinical Sciences &amp; Operations</last_name>
    <role>Study Director</role>
    <affiliation>Sanofi</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Investigational Site Number :840003</name>
      <address>
        <city>Cullman</city>
        <state>Alabama</state>
        <zip>35058</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :840012</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33609-4052</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :840002</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :840004</name>
      <address>
        <city>Raleigh</city>
        <state>North Carolina</state>
        <zip>27607</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :056002</name>
      <address>
        <city>Gent</city>
        <zip>9000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :056001</name>
      <address>
        <city>Leuven</city>
        <zip>3000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :100001</name>
      <address>
        <city>Sofia</city>
        <zip>1113</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :124001</name>
      <address>
        <city>Calgary</city>
        <state>Alberta</state>
        <zip>T3B 6A8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :156001</name>
      <address>
        <city>Beijing</city>
        <zip>100034</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :156002</name>
      <address>
        <city>Beijing</city>
        <zip>100045</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :156010</name>
      <address>
        <city>Beijing</city>
        <zip>100730</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :156006</name>
      <address>
        <city>Changchun</city>
        <zip>130021</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :156007</name>
      <address>
        <city>Changsha</city>
        <zip>410011</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :156008</name>
      <address>
        <city>Chengdu</city>
        <zip>610041</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :156005</name>
      <address>
        <city>Chongqing</city>
        <zip>400014</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :156012</name>
      <address>
        <city>Guangzhou</city>
        <zip>510630</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :156003</name>
      <address>
        <city>Shanghai</city>
        <zip>200092</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :156004</name>
      <address>
        <city>Shanghai</city>
        <zip>201102</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :156011</name>
      <address>
        <city>Shijiazhuang</city>
        <zip>050000</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :156009</name>
      <address>
        <city>Taiyuan</city>
        <zip>030001</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :233001</name>
      <address>
        <city>Tallinn</city>
        <zip>10617</zip>
        <country>Estonia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :250001</name>
      <address>
        <city>Le Kremlin Bicetre</city>
        <zip>94270</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :250002</name>
      <address>
        <city>Lyon Cedex 03</city>
        <zip>69394</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :250003</name>
      <address>
        <city>Rennes Cedex</city>
        <zip>35033</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :250005</name>
      <address>
        <city>Toulouse</city>
        <zip>31059</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :300002</name>
      <address>
        <city>Athens</city>
        <zip>115 27</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :300001</name>
      <address>
        <city>Thessaloniki</city>
        <zip>54642</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :376001</name>
      <address>
        <city>Jerusalem</city>
        <zip>91120</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :376003</name>
      <address>
        <city>Tel HaShomer</city>
        <zip>52621</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :422001</name>
      <address>
        <city>Beirut</city>
        <country>Lebanon</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :440001</name>
      <address>
        <city>Kaunas</city>
        <zip>50161</zip>
        <country>Lithuania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :504004</name>
      <address>
        <city>FES</city>
        <country>Morocco</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :504005</name>
      <address>
        <city>Marrakech</city>
        <zip>40000</zip>
        <country>Morocco</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :528001</name>
      <address>
        <city>Rotterdam</city>
        <zip>3015 CN</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :620001</name>
      <address>
        <city>Coimbra</city>
        <zip>3000-075</zip>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :643001</name>
      <address>
        <city>Moscow</city>
        <zip>127566</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :643003</name>
      <address>
        <city>Nizhny Novgorod</city>
        <zip>603155</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :643004</name>
      <address>
        <city>Novosibirsk</city>
        <zip>630087</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :643005</name>
      <address>
        <city>Saint-Petersburg</city>
        <zip>197022</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :643002</name>
      <address>
        <city>Saint-Petersburg</city>
        <zip>197110</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :688002</name>
      <address>
        <city>Belgrade</city>
        <zip>11000</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :724002</name>
      <address>
        <city>Murcia</city>
        <zip>30120</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :788001</name>
      <address>
        <city>La Manouba</city>
        <zip>2020</zip>
        <country>Tunisia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :788002</name>
      <address>
        <city>Sfax</city>
        <zip>3029</zip>
        <country>Tunisia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :788004</name>
      <address>
        <city>Sfax</city>
        <zip>3029</zip>
        <country>Tunisia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :792002</name>
      <address>
        <city>Ankara</city>
        <zip>06100</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :792001</name>
      <address>
        <city>Ankara</city>
        <zip>06500</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :792006</name>
      <address>
        <city>Istanbul</city>
        <zip>34390</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :792003</name>
      <address>
        <city>Istanbul</city>
        <zip>34688</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :792008</name>
      <address>
        <city>Izmir</city>
        <zip>35210</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :792007</name>
      <address>
        <city>İzmir</city>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :804001</name>
      <address>
        <city>Kharkiv</city>
        <zip>61068</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :804002</name>
      <address>
        <city>Kharkiv</city>
        <zip>61068</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :826001</name>
      <address>
        <city>London</city>
        <state>London, City Of</state>
        <zip>SE1 7EH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :826003</name>
      <address>
        <city>Birmingham</city>
        <zip>B4 6NH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
    <country>Bulgaria</country>
    <country>Canada</country>
    <country>China</country>
    <country>Estonia</country>
    <country>France</country>
    <country>Greece</country>
    <country>Israel</country>
    <country>Lebanon</country>
    <country>Lithuania</country>
    <country>Morocco</country>
    <country>Netherlands</country>
    <country>Portugal</country>
    <country>Russian Federation</country>
    <country>Serbia</country>
    <country>Spain</country>
    <country>Tunisia</country>
    <country>Turkey</country>
    <country>Ukraine</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Australia</country>
    <country>Macedonia, The Former Yugoslav Republic of</country>
    <country>North Macedonia</country>
    <country>Poland</country>
    <country>Slovenia</country>
  </removed_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>July 17, 2014</study_first_submitted>
  <study_first_submitted_qc>July 24, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 25, 2014</study_first_posted>
  <results_first_submitted>October 20, 2020</results_first_submitted>
  <results_first_submitted_qc>November 27, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">November 30, 2020</results_first_posted>
  <last_update_submitted>August 30, 2023</last_update_submitted>
  <last_update_submitted_qc>August 30, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 1, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Multiple Sclerosis</mesh_term>
    <mesh_term>Sclerosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Teriflunomide</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org</ipd_description>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>December 10, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/08/NCT02201108/Prot_002.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 28, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/08/NCT02201108/SAP_003.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Study was conducted at 57 active centers in 21 countries. A total of 185 participants were screened between 16 July 2014 and 27 December 2017, of which 166 participants were enrolled and randomized. A total of 19 participants failed screening mainly due to meeting exclusion criteria.</recruitment_details>
      <pre_assignment_details>Participants were randomly assigned to receive either teriflunomide or placebo in a 2:1 ratio via Interactive Voice Response System. Randomization was stratified by the country and participant's pubertal status.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Placebo/Teriflunomide</title>
          <description>Participants received Placebo matching to teriflunomide tablet orally once daily for 96 weeks in double blind (DB) treatment period. After completion of DB period, eligible participants entered in open label (OL) period and received 1 teriflunomide tablet, 3.5 milligrams (mg) (in case of body weight [BW] up to 40 kilograms [kg]) or 7 mg (BW greater than [&gt;] 40 kg) for first 8 weeks. After 8 weeks if individual predicted PK parameter was less than or equal to (&lt;=) 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW&gt;40 kg) in the OL period for additional 96 weeks (i.e., up to Week 192). If individual predicted PK parameters &gt;95th percentile of adult range then participant received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW &gt;40 kg).The adult range (5th-95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as maximum concentration observed (Cmax) ranging from 8.03 to 49.10 micrograms per milliliter (mcg/mL) and area under the curve from time 0 hour to 24 hours (AUC0-24) ranging from 184 to 1160 micrograms*hour per milliliter (mcg*h/mL).</description>
        </group>
        <group group_id="P2">
          <title>Teriflunomide/Teriflunomide</title>
          <description>Participants received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW &gt;40 kg) orally once daily for 8 weeks. After 8 weeks, based on individual predicted PK parameters, teriflunomide was administered in following manner up to 96 weeks: if predicted PK parameters &lt;= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW &gt;40 kg); or if individual predicted PK parameters &gt;95th percentile of adult range then participants received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW &gt;40 kg). The adult range (5th - 95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL. After completion of DB period, eligible participants entered in OL period and continued receiving teriflunomide at the same dose in the OL period for additional 96 weeks (i.e., up to Week 192).</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Double-blind Period (up to Week 96)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="57"/>
                <participants group_id="P2" count="109"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="53"/>
                <participants group_id="P2" count="102"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="7"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="6"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <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="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Open Label Period (up to Week 192)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="52"/>
                <participants group_id="P2" count="100"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="31"/>
                <participants group_id="P2" count="73"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="21"/>
                <participants group_id="P2" count="27"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="14"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Poor compliance to protocol</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other reason</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="7"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Analysis was performed on all randomized participants.</population>
      <group_list>
        <group group_id="B1">
          <title>Placebo/Teriflunomide</title>
          <description>Participants received Placebo matching to teriflunomide tablet orally once daily for 96 weeks in DB treatment period. After completion of DB period, eligible participants entered in OL period and received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW &gt;40 kg) for first 8 weeks. After 8 weeks if individual predicted PK parameter was &lt;= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW&gt;40 kg) in the OL period for additional 96 weeks (i.e., up to Week 192). If individual predicted PK parameters &gt;95th percentile of adult range then participant received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW &gt;40 kg). The adult range (5th-95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL.</description>
        </group>
        <group group_id="B2">
          <title>Teriflunomide/Teriflunomide</title>
          <description>Participants received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW &gt;40 kg) orally once daily for 8 weeks. After 8 weeks, based on individual predicted PK parameters, teriflunomide was administered in following manner up to 96 weeks: if predicted PK parameters &lt;= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW &gt;40 kg); or if individual predicted PK parameters &gt;95th percentile of adult range then participants received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW &gt;40 kg). The adult range (5th - 95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL. After completion of DB period, eligible participants entered in OL period and continued receiving teriflunomide at the same dose in the OL period for additional 96 weeks (i.e., up to Week 192).</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="57"/>
            <count group_id="B2" value="109"/>
            <count group_id="B3" value="166"/>
          </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="14.7" spread="2.1"/>
                    <measurement group_id="B2" value="14.6" spread="2.0"/>
                    <measurement group_id="B3" value="14.6" spread="2.0"/>
                  </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="39"/>
                    <measurement group_id="B2" value="72"/>
                    <measurement group_id="B3" value="111"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="37"/>
                    <measurement group_id="B3" value="55"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Race</title>
              <category_list>
                <category>
                  <title>Caucasian/White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="42"/>
                    <measurement group_id="B2" value="75"/>
                    <measurement group_id="B3" value="117"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian/Oriental</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="25"/>
                    <measurement group_id="B3" value="37"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Other</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Time to First Confirmed Clinical Relapse</title>
        <description>Time to first clinical relapse was defined as the duration (in weeks) between randomization and first confirmed clinical relapse. Clinical relapses were defined as new or recurrent neurological symptoms not associated with fever or infection, lasting at least 24 hours, and accompanied by new objective neurological findings upon neurological examination and documented by a standardized, quantified functional system score (FSSs) which included 8 items and items were rated on different scales: brain stem, cerebellar and cerebral functions rated on a scale of 0 to 5; visual, pyramidal, sensory and bowel/bladder rated on a scale of 0 to 6 and ambulation on a scale of 0 to 12, where higher score in each scale indicated worsened neurological function. Confirmed clinical relapse were reviewed and confirmed by an independent Relapse Adjudication Panel (RAP). A participant without confirmed clinical relapse, was considered as clinical relapse free until the end of Week 96.</description>
        <time_frame>Baseline up to Week 96</time_frame>
        <population>Analysis was performed on Intent-to-treat (ITT) population, which consisted of all randomized participants analyzed according to the treatment allocated by randomization.</population>
        <group_list>
          <group group_id="O1">
            <title>Double-Blind Treatment Period: Placebo</title>
            <description>Participants received Placebo matching to teriflunomide tablet orally once daily for 96 weeks in DB period.</description>
          </group>
          <group group_id="O2">
            <title>Double-Blind Treatment Period: Teriflunomide</title>
            <description>Participants received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW &gt;40 kg) orally once daily for 8 weeks. After 8 weeks, based on individual predicted PK parameters, teriflunomide was administered in following manner up to 96 weeks: if predicted PK parameters &lt;= 95th percentile of adult range after 7 mg once daily: 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW &gt;40 kg); or if individual predicted PK parameters &gt;95th percentile of adult range then participants received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW &gt;40 kg). The adult range (5th - 95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL in DB period.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to First Confirmed Clinical Relapse</title>
          <description>Time to first clinical relapse was defined as the duration (in weeks) between randomization and first confirmed clinical relapse. Clinical relapses were defined as new or recurrent neurological symptoms not associated with fever or infection, lasting at least 24 hours, and accompanied by new objective neurological findings upon neurological examination and documented by a standardized, quantified functional system score (FSSs) which included 8 items and items were rated on different scales: brain stem, cerebellar and cerebral functions rated on a scale of 0 to 5; visual, pyramidal, sensory and bowel/bladder rated on a scale of 0 to 6 and ambulation on a scale of 0 to 12, where higher score in each scale indicated worsened neurological function. Confirmed clinical relapse were reviewed and confirmed by an independent Relapse Adjudication Panel (RAP). A participant without confirmed clinical relapse, was considered as clinical relapse free until the end of Week 96.</description>
          <population>Analysis was performed on Intent-to-treat (ITT) population, which consisted of all randomized participants analyzed according to the treatment allocated by randomization.</population>
          <units>weeks</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="57"/>
                <count group_id="O2" value="109"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="39.14" lower_limit="0.1" upper_limit="98.0"/>
                    <measurement group_id="O2" value="75.29" lower_limit="0.1" upper_limit="98.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.2949</p_value>
            <p_value_desc>Threshold for significance was &lt; 0.05.</p_value_desc>
            <method>Stratified Log-Rank test</method>
            <method_desc>P-value derived from log-rank test with stratification of region and pubertal status.</method_desc>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.657</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.388</ci_lower_limit>
            <ci_upper_limit>1.113</ci_upper_limit>
            <estimate_desc>Hazard ratio was estimated using a Cox proportional-hazards model with factors for treatment group, region, pubertal status, age, and number of relapses in the year prior to randomization as covariates and with robust variance estimation.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Probability of Participants Who Were Clinical Relapse Free at Weeks 24, 48, 72, 96, 120, 144, 168 and 192</title>
        <description>Participant was considered free of clinical relapse if the participant had no confirmed clinical relapse before treatment discontinuation/completion in 192 weeks treatment period. Clinical relapses: new/recurrent neurological symptoms not associated with fever/infection, lasted at least 24 hours, and accompanied by new objective neurological findings upon neurological examination and documented by standardized, quantified FSSs which included 8 items: rated on different scales: brain stem, cerebellar and cerebral functions rated on scale of 0 to 5; visual, pyramidal, sensory and bowel/bladder rated on scale of 0 to 6 &amp; ambulation on scale of 0 to 12, where higher score in each scale indicated worsened neurological function. New/recurrent symptoms occurred less than 30 days following onset of relapse were considered part of same relapse. Probability of participants who were clinical relapse free at specified weeks were estimated by Kaplan-Meier method and reported.</description>
        <time_frame>Weeks 24, 48, 72, 96, 120, 144, 168 and 192</time_frame>
        <population>Analysis was performed on efficacy population which included all participants enrolled and treated with at least 1 dose of teriflunomide in OL period analyzed according to the treatment group allocated by randomization in the DB period.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo/Teriflunomide</title>
            <description>Participants received Placebo matching to teriflunomide tablet orally once daily for 96 weeks in DB treatment period. After completion of DB period, eligible participants entered in OL period and received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW &gt;40 kg) for first 8 weeks. After 8 weeks if individual predicted PK parameter was &lt;= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW&gt;40 kg) in the OL period for additional 96 weeks (i.e., up to Week 192). If individual predicted PK parameters &gt;95th percentile of adult range then participant received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW &gt;40 kg). The adult range (5th-95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL.</description>
          </group>
          <group group_id="O2">
            <title>Teriflunomide/ Teriflunomide</title>
            <description>Participants received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW &gt;40 kg) orally once daily for 8 weeks. After 8 weeks, based on individual predicted PK parameters, teriflunomide was administered in following manner up to 96 weeks: if predicted PK parameters &lt;= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW &gt;40 kg); or if individual predicted PK parameters &gt;95th percentile of adult range then participants received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW &gt;40 kg). The adult range (5th - 95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL. After completion of DB period, eligible participants entered in OL period and continued receiving teriflunomide at the same dose in the OL period for additional 96 weeks (i.e., up to Week 192).</description>
          </group>
        </group_list>
        <measure>
          <title>Probability of Participants Who Were Clinical Relapse Free at Weeks 24, 48, 72, 96, 120, 144, 168 and 192</title>
          <description>Participant was considered free of clinical relapse if the participant had no confirmed clinical relapse before treatment discontinuation/completion in 192 weeks treatment period. Clinical relapses: new/recurrent neurological symptoms not associated with fever/infection, lasted at least 24 hours, and accompanied by new objective neurological findings upon neurological examination and documented by standardized, quantified FSSs which included 8 items: rated on different scales: brain stem, cerebellar and cerebral functions rated on scale of 0 to 5; visual, pyramidal, sensory and bowel/bladder rated on scale of 0 to 6 &amp; ambulation on scale of 0 to 12, where higher score in each scale indicated worsened neurological function. New/recurrent symptoms occurred less than 30 days following onset of relapse were considered part of same relapse. Probability of participants who were clinical relapse free at specified weeks were estimated by Kaplan-Meier method and reported.</description>
          <population>Analysis was performed on efficacy population which included all participants enrolled and treated with at least 1 dose of teriflunomide in OL period analyzed according to the treatment group allocated by randomization in the DB period.</population>
          <units>probability of relapse free participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="52"/>
                <count group_id="O2" value="100"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 24</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.750" lower_limit="0.609" upper_limit="0.846"/>
                    <measurement group_id="O2" value="0.820" lower_limit="0.730" upper_limit="0.883"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 48</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.596" lower_limit="0.451" upper_limit="0.715"/>
                    <measurement group_id="O2" value="0.700" lower_limit="0.600" upper_limit="0.780"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 72</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.519" lower_limit="0.377" upper_limit="0.644"/>
                    <measurement group_id="O2" value="0.630" lower_limit="0.528" upper_limit="0.716"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 96</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.442" lower_limit="0.305" upper_limit="0.571"/>
                    <measurement group_id="O2" value="0.600" lower_limit="0.497" upper_limit="0.688"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 120</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.404" lower_limit="0.271" upper_limit="0.533"/>
                    <measurement group_id="O2" value="0.570" lower_limit="0.467" upper_limit="0.660"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 144</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.365" lower_limit="0.238" upper_limit="0.494"/>
                    <measurement group_id="O2" value="0.540" lower_limit="0.437" upper_limit="0.631"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 168</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.365" lower_limit="0.238" upper_limit="0.494"/>
                    <measurement group_id="O2" value="0.518" lower_limit="0.416" upper_limit="0.611"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 192</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.365" lower_limit="0.238" upper_limit="0.494"/>
                    <measurement group_id="O2" value="0.518" lower_limit="0.416" upper_limit="0.611"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Brain Magnetic Resonance Imaging (MRI) Assessment: Number of New or Enlarged T2 Lesions Per MRI Scan</title>
        <description>Number of new or enlarged T2 lesions per scan was defined as the total number of new or enlarged T2 lesion that occurred during the 192 weeks treatment period divided by the total number of scans performed during 192 weeks. To account for the different numbers of scans performed among the participants, a negative binomial regression model with robust variance estimation was used. The model included the total number of new or enlarged T2-lesions as the response variable, with treatment group, region, pubertal status and age as covariates and log-transformed number of scans as an offset variable.</description>
        <time_frame>Baseline up to Week 192</time_frame>
        <population>Analysis was performed on efficacy population.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo/Teriflunomide</title>
            <description>Participants received Placebo matching to teriflunomide tablet orally once daily for 96 weeks in DB treatment period. After completion of DB period, eligible participants entered in OL period and received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW &gt;40 kg) for first 8 weeks. After 8 weeks if individual predicted PK parameter was &lt;= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW&gt;40 kg) in the OL period for additional 96 weeks (i.e., up to Week 192). If individual predicted PK parameters &gt;95th percentile of adult range then participant received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW &gt;40 kg). The adult range (5th-95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL.</description>
          </group>
          <group group_id="O2">
            <title>Teriflunomide/ Teriflunomide</title>
            <description>Participants received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW &gt;40 kg) orally once daily for 8 weeks. After 8 weeks, based on individual predicted PK parameters, teriflunomide was administered in following manner up to 96 weeks: if predicted PK parameters &lt;= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW &gt;40 kg); or if individual predicted PK parameters &gt;95th percentile of adult range then participants received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW &gt;40 kg). The adult range (5th - 95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL. After completion of DB period, eligible participants entered in OL period and continued receiving teriflunomide at the same dose in the OL period for additional 96 weeks (i.e., up to Week 192).</description>
          </group>
        </group_list>
        <measure>
          <title>Brain Magnetic Resonance Imaging (MRI) Assessment: Number of New or Enlarged T2 Lesions Per MRI Scan</title>
          <description>Number of new or enlarged T2 lesions per scan was defined as the total number of new or enlarged T2 lesion that occurred during the 192 weeks treatment period divided by the total number of scans performed during 192 weeks. To account for the different numbers of scans performed among the participants, a negative binomial regression model with robust variance estimation was used. The model included the total number of new or enlarged T2-lesions as the response variable, with treatment group, region, pubertal status and age as covariates and log-transformed number of scans as an offset variable.</description>
          <population>Analysis was performed on efficacy population.</population>
          <units>lesions per scan</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="52"/>
                <count group_id="O2" value="100"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.087" lower_limit="6.586" upper_limit="18.662"/>
                    <measurement group_id="O2" value="5.664" lower_limit="3.417" upper_limit="9.389"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Relative risk ratio</param_type>
            <param_value>0.511</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.343</ci_lower_limit>
            <ci_upper_limit>0.762</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Brain Magnetic Resonance Imaging Assessment: Number of T1 Gadolinium (Gd)-Enhancing T1 Lesions Per MRI Scan</title>
        <description>The number of T1 Gd-Enhancing lesions per scan was defined as the total number of Gd-enhancing lesions that occurred during the 192 weeks treatment period divided by the total number of scans performed during 192 weeks. To account for the different number of scans performed among the participants, a negative binomial regression model with robust variance estimation was used. The model included the total number of T1-lesions as the response variable, with treatment group, region, pubertal status and age as covariates and log-transformed number of scans as an offset variable.</description>
        <time_frame>Baseline up to Week 192</time_frame>
        <population>Analysis was performed on efficacy population.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo/Teriflunomide</title>
            <description>Participants received Placebo matching to teriflunomide tablet orally once daily for 96 weeks in DB treatment period. After completion of DB period, eligible participants entered in OL period and received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW &gt;40 kg) for first 8 weeks. After 8 weeks if individual predicted PK parameter was &lt;= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW&gt;40 kg) in the OL period for additional 96 weeks (i.e., up to Week 192). If individual predicted PK parameters &gt;95th percentile of adult range then participant received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW &gt;40 kg). The adult range (5th-95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL.</description>
          </group>
          <group group_id="O2">
            <title>Teriflunomide/ Teriflunomide</title>
            <description>Participants received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW &gt;40 kg) orally once daily for 8 weeks. After 8 weeks, based on individual predicted PK parameters, teriflunomide was administered in following manner up to 96 weeks: if predicted PK parameters &lt;= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW &gt;40 kg); or if individual predicted PK parameters &gt;95th percentile of adult range then participants received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW &gt;40 kg). The adult range (5th - 95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL. After completion of DB period, eligible participants entered in OL period and continued receiving teriflunomide at the same dose in the OL period for additional 96 weeks (i.e., up to Week 192).</description>
          </group>
        </group_list>
        <measure>
          <title>Brain Magnetic Resonance Imaging Assessment: Number of T1 Gadolinium (Gd)-Enhancing T1 Lesions Per MRI Scan</title>
          <description>The number of T1 Gd-Enhancing lesions per scan was defined as the total number of Gd-enhancing lesions that occurred during the 192 weeks treatment period divided by the total number of scans performed during 192 weeks. To account for the different number of scans performed among the participants, a negative binomial regression model with robust variance estimation was used. The model included the total number of T1-lesions as the response variable, with treatment group, region, pubertal status and age as covariates and log-transformed number of scans as an offset variable.</description>
          <population>Analysis was performed on efficacy population.</population>
          <units>lesions per scan</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="52"/>
                <count group_id="O2" value="100"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.686" lower_limit="1.263" upper_limit="5.712"/>
                    <measurement group_id="O2" value="1.532" lower_limit="0.624" upper_limit="3.762"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Relative risk ratio</param_type>
            <param_value>0.57</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.331</ci_lower_limit>
            <ci_upper_limit>0.983</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Brain Magnetic Resonance Imaging Assessment: Change From Baseline in Volume of T2 Lesions at Weeks 24, 36, 48, 72, 96, 144 and 192</title>
        <description>Volume of T2 lesions was measured by MRI scan.</description>
        <time_frame>Baseline, DB period: Weeks 24, 36, 48, 72 and 96; OL period: Weeks 48, 96, 144 and 192</time_frame>
        <population>Analysis was performed on efficacy population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo/Teriflunomide</title>
            <description>Participants received Placebo matching to teriflunomide tablet orally once daily for 96 weeks in DB treatment period. After completion of DB period, eligible participants entered in OL period and received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW &gt;40 kg) for first 8 weeks. After 8 weeks if individual predicted PK parameter was &lt;= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW&gt;40 kg) in the OL period for additional 96 weeks (i.e., up to Week 192). If individual predicted PK parameters &gt;95th percentile of adult range then participant received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW &gt;40 kg). The adult range (5th-95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL.</description>
          </group>
          <group group_id="O2">
            <title>Teriflunomide/ Teriflunomide</title>
            <description>Participants received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW &gt;40 kg) orally once daily for 8 weeks. After 8 weeks, based on individual predicted PK parameters, teriflunomide was administered in following manner up to 96 weeks: if predicted PK parameters &lt;= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW &gt;40 kg); or if individual predicted PK parameters &gt;95th percentile of adult range then participants received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW &gt;40 kg). The adult range (5th - 95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL. After completion of DB period, eligible participants entered in OL period and continued receiving teriflunomide at the same dose in the OL period for additional 96 weeks (i.e., up to Week 192).</description>
          </group>
        </group_list>
        <measure>
          <title>Brain Magnetic Resonance Imaging Assessment: Change From Baseline in Volume of T2 Lesions at Weeks 24, 36, 48, 72, 96, 144 and 192</title>
          <description>Volume of T2 lesions was measured by MRI scan.</description>
          <population>Analysis was performed on efficacy population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.</population>
          <units>milliliters</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="52"/>
                <count group_id="O2" value="98"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>DB Period: Week 24</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="40"/>
                    <count group_id="O2" value="88"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.0" spread="7.0"/>
                    <measurement group_id="O2" value="0.5" spread="1.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DB Period: Week 36</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="39"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.6" spread="11.7"/>
                    <measurement group_id="O2" value="4.4" spread="21.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DB Period: Week 48</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="68"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.5" spread="0.6"/>
                    <measurement group_id="O2" value="-0.2" spread="3.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DB Period: Week 72</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="16"/>
                    <count group_id="O2" value="59"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.2" spread="1.6"/>
                    <measurement group_id="O2" value="0.1" spread="1.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DB Period: Week 96</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="14"/>
                    <count group_id="O2" value="51"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.9" spread="1.4"/>
                    <measurement group_id="O2" value="0.2" spread="1.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>OL Period: Week 48</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="51"/>
                    <count group_id="O2" value="88"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.0" spread="9.7"/>
                    <measurement group_id="O2" value="0.6" spread="8.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>OL Period: Week 96</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="37"/>
                    <count group_id="O2" value="74"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.7" spread="8.1"/>
                    <measurement group_id="O2" value="1.9" spread="4.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>OL Period: Week 144</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="20"/>
                    <count group_id="O2" value="23"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.7" spread="10.7"/>
                    <measurement group_id="O2" value="0.4" spread="17.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>OL Period: Week 192</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                    <count group_id="O2" value="8"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.4" spread="9.4"/>
                    <measurement group_id="O2" value="-3.6" spread="30.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Brain Magnetic Resonance Imaging Assessment: Change From Baseline in Volume of T1 Hypointense Lesions</title>
        <description>Volume of T1 hypointense lesions was measured by MRI scan.</description>
        <time_frame>Baseline, DB period: Weeks 24, 36, 48, 72 and 96; OL period: Weeks 48, 96, 144 and 192</time_frame>
        <population>Analysis was performed on efficacy population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo/Teriflunomide</title>
            <description>Participants received Placebo matching to teriflunomide tablet orally once daily for 96 weeks in DB treatment period. After completion of DB period, eligible participants entered in OL period and received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW &gt;40 kg) for first 8 weeks. After 8 weeks if individual predicted PK parameter was &lt;= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW&gt;40 kg) in the OL period for additional 96 weeks (i.e., up to Week 192). If individual predicted PK parameters &gt;95th percentile of adult range then participant received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW &gt;40 kg). The adult range (5th-95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL.</description>
          </group>
          <group group_id="O2">
            <title>Teriflunomide/ Teriflunomide</title>
            <description>Participants received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW &gt;40 kg) orally once daily for 8 weeks. After 8 weeks, based on individual predicted PK parameters, teriflunomide was administered in following manner up to 96 weeks: if predicted PK parameters &lt;= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW &gt;40 kg); or if individual predicted PK parameters &gt;95th percentile of adult range then participants received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW &gt;40 kg). The adult range (5th - 95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL. After completion of DB period, eligible participants entered in OL period and continued receiving teriflunomide at the same dose in the OL period for additional 96 weeks (i.e., up to Week 192).</description>
          </group>
        </group_list>
        <measure>
          <title>Brain Magnetic Resonance Imaging Assessment: Change From Baseline in Volume of T1 Hypointense Lesions</title>
          <description>Volume of T1 hypointense lesions was measured by MRI scan.</description>
          <population>Analysis was performed on efficacy population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.</population>
          <units>milliliters</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="52"/>
                <count group_id="O2" value="98"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>DB Period: Week 24</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="40"/>
                    <count group_id="O2" value="88"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.3" spread="1.3"/>
                    <measurement group_id="O2" value="0.0" spread="0.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DB Period: Week 36</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="39"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.8" spread="1.8"/>
                    <measurement group_id="O2" value="0.2" spread="0.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DB Period: Week 48</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="20"/>
                    <count group_id="O2" value="68"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.2" spread="0.4"/>
                    <measurement group_id="O2" value="0.4" spread="2.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DB Period: Week 72</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="16"/>
                    <count group_id="O2" value="58"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.1" spread="0.7"/>
                    <measurement group_id="O2" value="0.1" spread="0.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DB Period: Week 96</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="14"/>
                    <count group_id="O2" value="50"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.1" spread="0.6"/>
                    <measurement group_id="O2" value="0.1" spread="0.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>OL Period: Week 48</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="51"/>
                    <count group_id="O2" value="86"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.7" spread="1.9"/>
                    <measurement group_id="O2" value="0.5" spread="1.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>OL Period: Week 96</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="37"/>
                    <count group_id="O2" value="73"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.0" spread="2.0"/>
                    <measurement group_id="O2" value="0.6" spread="1.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>OL Period: Week 144</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="20"/>
                    <count group_id="O2" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.0" spread="3.0"/>
                    <measurement group_id="O2" value="1.9" spread="3.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>OL Period: Week 192</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                    <count group_id="O2" value="8"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.0" spread="5.8"/>
                    <measurement group_id="O2" value="2.5" spread="5.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Brain Magnetic Resonance Imaging Assessment: Number of New T1 Hypointense Lesions Per MRI Scan</title>
        <description>The number of new T1 hypointense lesions were obtained from MRI scans.</description>
        <time_frame>Baseline up to Week 192</time_frame>
        <population>Analysis was performed on efficacy population.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo/Teriflunomide</title>
            <description>Participants received Placebo matching to teriflunomide tablet orally once daily for 96 weeks in DB treatment period. After completion of DB period, eligible participants entered in OL period and received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW &gt;40 kg) for first 8 weeks. After 8 weeks if individual predicted PK parameter was &lt;= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW&gt;40 kg) in the OL period for additional 96 weeks (i.e., up to Week 192). If individual predicted PK parameters &gt;95th percentile of adult range then participant received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW &gt;40 kg). The adult range (5th-95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL.</description>
          </group>
          <group group_id="O2">
            <title>Teriflunomide/ Teriflunomide</title>
            <description>Participants received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW &gt;40 kg) orally once daily for 8 weeks. After 8 weeks, based on individual predicted PK parameters, teriflunomide was administered in following manner up to 96 weeks: if predicted PK parameters &lt;= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW &gt;40 kg); or if individual predicted PK parameters &gt;95th percentile of adult range then participants received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW &gt;40 kg). The adult range (5th - 95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL. After completion of DB period, eligible participants entered in OL period and continued receiving teriflunomide at the same dose in the OL period for additional 96 weeks (i.e., up to Week 192).</description>
          </group>
        </group_list>
        <measure>
          <title>Brain Magnetic Resonance Imaging Assessment: Number of New T1 Hypointense Lesions Per MRI Scan</title>
          <description>The number of new T1 hypointense lesions were obtained from MRI scans.</description>
          <population>Analysis was performed on efficacy population.</population>
          <units>lesions</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="52"/>
                <count group_id="O2" value="100"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1561"/>
                    <measurement group_id="O2" value="1910"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Relative risk ratio</param_type>
            <param_value>0.498</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.296</ci_lower_limit>
            <ci_upper_limit>0.836</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Brain Magnetic Resonance Imaging Assessment: Percentage of Participants Free of New or Enlarged MRI T2-Lesions</title>
        <description>Percentage of participants who were free of new or enlarged T2 lesions at Weeks 24, 48, 72, 96, 144 and 192 were reported.</description>
        <time_frame>Baseline, Weeks 24, 48, 72, 96, 144 and 192</time_frame>
        <population>Analysis was performed on efficacy population.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo/Teriflunomide</title>
            <description>Participants received Placebo matching to teriflunomide tablet orally once daily for 96 weeks in DB treatment period. After completion of DB period, eligible participants entered in OL period and received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW &gt;40 kg) for first 8 weeks. After 8 weeks if individual predicted PK parameter was &lt;= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW&gt;40 kg) in the OL period for additional 96 weeks (i.e., up to Week 192). If individual predicted PK parameters &gt;95th percentile of adult range then participant received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW &gt;40 kg). The adult range (5th-95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL.</description>
          </group>
          <group group_id="O2">
            <title>Teriflunomide/ Teriflunomide</title>
            <description>Participants received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW &gt;40 kg) orally once daily for 8 weeks. After 8 weeks, based on individual predicted PK parameters, teriflunomide was administered in following manner up to 96 weeks: if predicted PK parameters &lt;= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW &gt;40 kg); or if individual predicted PK parameters &gt;95th percentile of adult range then participants received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW &gt;40 kg). The adult range (5th - 95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL. After completion of DB period, eligible participants entered in OL period and continued receiving teriflunomide at the same dose in the OL period for additional 96 weeks (i.e., up to Week 192).</description>
          </group>
        </group_list>
        <measure>
          <title>Brain Magnetic Resonance Imaging Assessment: Percentage of Participants Free of New or Enlarged MRI T2-Lesions</title>
          <description>Percentage of participants who were free of new or enlarged T2 lesions at Weeks 24, 48, 72, 96, 144 and 192 were reported.</description>
          <population>Analysis was performed on efficacy population.</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="52"/>
                <count group_id="O2" value="100"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 24</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="86.5"/>
                    <measurement group_id="O2" value="86.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 48</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="32.7"/>
                    <measurement group_id="O2" value="25.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 72</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15.4"/>
                    <measurement group_id="O2" value="17.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 96</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15.4"/>
                    <measurement group_id="O2" value="16.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 144</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.5"/>
                    <measurement group_id="O2" value="14.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 192</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.7"/>
                    <measurement group_id="O2" value="9.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Brain Magnetic Resonance Imaging Assessment: Percent Change From Baseline in Brain Volume at Weeks 24, 36, 48, 72, 96, 144 and 192</title>
        <description>Percent change from baseline in brain volume (assessed using MRI scans of the Brain) at Weeks 24, 36, 48,72, 96, 144 and 192 was reported.</description>
        <time_frame>Baseline, DB period: Weeks 24, 36, 48, 72 and 96; OL period: Weeks 48, 96, 144 and 192</time_frame>
        <population>Analysis was performed on efficacy population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo/Teriflunomide</title>
            <description>Participants received Placebo matching to teriflunomide tablet orally once daily for 96 weeks in DB treatment period. After completion of DB period, eligible participants entered in OL period and received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW &gt;40 kg) for first 8 weeks. After 8 weeks if individual predicted PK parameter was &lt;= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW&gt;40 kg) in the OL period for additional 96 weeks (i.e., up to Week 192). If individual predicted PK parameters &gt;95th percentile of adult range then participant received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW &gt;40 kg). The adult range (5th-95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL.</description>
          </group>
          <group group_id="O2">
            <title>Teriflunomide/ Teriflunomide</title>
            <description>Participants received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW &gt;40 kg) orally once daily for 8 weeks. After 8 weeks, based on individual predicted PK parameters, teriflunomide was administered in following manner up to 96 weeks: if predicted PK parameters &lt;= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW &gt;40 kg); or if individual predicted PK parameters &gt;95th percentile of adult range then participants received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW &gt;40 kg). The adult range (5th - 95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL. After completion of DB period, eligible participants entered in OL period and continued receiving teriflunomide at the same dose in the OL period for additional 96 weeks (i.e., up to Week 192).</description>
          </group>
        </group_list>
        <measure>
          <title>Brain Magnetic Resonance Imaging Assessment: Percent Change From Baseline in Brain Volume at Weeks 24, 36, 48, 72, 96, 144 and 192</title>
          <description>Percent change from baseline in brain volume (assessed using MRI scans of the Brain) at Weeks 24, 36, 48,72, 96, 144 and 192 was reported.</description>
          <population>Analysis was performed on efficacy population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.</population>
          <units>percent change</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="52"/>
                <count group_id="O2" value="97"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>DB Period: Week 24</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="38"/>
                    <count group_id="O2" value="83"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.3" spread="0.7"/>
                    <measurement group_id="O2" value="-0.2" spread="0.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DB Period: Week 36</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="17"/>
                    <count group_id="O2" value="39"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.7" spread="0.7"/>
                    <measurement group_id="O2" value="-0.4" spread="1.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DB Period: Week 48</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="20"/>
                    <count group_id="O2" value="64"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.6" spread="1.1"/>
                    <measurement group_id="O2" value="-0.5" spread="0.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DB Period: Week 72</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="16"/>
                    <count group_id="O2" value="53"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.9" spread="1.3"/>
                    <measurement group_id="O2" value="-0.6" spread="1.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DB Period: Week 96</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="13"/>
                    <count group_id="O2" value="47"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.9" spread="1.3"/>
                    <measurement group_id="O2" value="-0.8" spread="1.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>OL Period: Week 48</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="43"/>
                    <count group_id="O2" value="73"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.4" spread="1.6"/>
                    <measurement group_id="O2" value="-1.1" spread="1.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>OL Period: Week 96</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="33"/>
                    <count group_id="O2" value="60"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.8" spread="1.9"/>
                    <measurement group_id="O2" value="-1.4" spread="1.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>OL Period: Week 144</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="16"/>
                    <count group_id="O2" value="17"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.1" spread="2.8"/>
                    <measurement group_id="O2" value="-2.0" spread="1.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>OL Period: Week 192</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.2" spread="1.2"/>
                    <measurement group_id="O2" value="-3.0" spread="1.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cognitive Assessment: Change From Baseline in Total Number of Correct Substitutions Measured by Symbol Digit Modalities Test (SDMT) at Weeks 24, 48, 72, 96, 120, 144, 168 and 192</title>
        <description>SDMT measures the time to pair abstract symbols with specific numbers. It is a simple substitution task that gives the examinee 90 seconds to pair specific numbers with given geometric figures as a measure for screening cognitive impairment. The SDMT score is the number of correct substitution and ranged from 0 (worst outcome) to 110 (best outcome), where higher score indicated better cognitive function.</description>
        <time_frame>Baseline, DB period: Weeks 24, 48, 72 and 96; OL period: Weeks 24, 48, 72, 96, 120, 144, 168 and 192</time_frame>
        <population>Analysis was performed on efficacy population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo/Teriflunomide</title>
            <description>Participants received Placebo matching to teriflunomide tablet orally once daily for 96 weeks in DB treatment period. After completion of DB period, eligible participants entered in OL period and received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW &gt;40 kg) for first 8 weeks. After 8 weeks if individual predicted PK parameter was &lt;= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW&gt;40 kg) in the OL period for additional 96 weeks (i.e., up to Week 192). If individual predicted PK parameters &gt;95th percentile of adult range then participant received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW &gt;40 kg). The adult range (5th-95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL.</description>
          </group>
          <group group_id="O2">
            <title>Teriflunomide/ Teriflunomide</title>
            <description>Participants received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW &gt;40 kg) orally once daily for 8 weeks. After 8 weeks, based on individual predicted PK parameters, teriflunomide was administered in following manner up to 96 weeks: if predicted PK parameters &lt;= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW &gt;40 kg); or if individual predicted PK parameters &gt;95th percentile of adult range then participants received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW &gt;40 kg). The adult range (5th - 95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL. After completion of DB period, eligible participants entered in OL period and continued receiving teriflunomide at the same dose in the OL period for additional 96 weeks (i.e., up to Week 192).</description>
          </group>
        </group_list>
        <measure>
          <title>Cognitive Assessment: Change From Baseline in Total Number of Correct Substitutions Measured by Symbol Digit Modalities Test (SDMT) at Weeks 24, 48, 72, 96, 120, 144, 168 and 192</title>
          <description>SDMT measures the time to pair abstract symbols with specific numbers. It is a simple substitution task that gives the examinee 90 seconds to pair specific numbers with given geometric figures as a measure for screening cognitive impairment. The SDMT score is the number of correct substitution and ranged from 0 (worst outcome) to 110 (best outcome), where higher score indicated better cognitive function.</description>
          <population>Analysis was performed on efficacy population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="51"/>
                <count group_id="O2" value="96"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>DB Period: Week 24</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="40"/>
                    <count group_id="O2" value="85"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.1" spread="12.0"/>
                    <measurement group_id="O2" value="4.6" spread="9.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DB Period: Week 48</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="20"/>
                    <count group_id="O2" value="64"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.3" spread="14.1"/>
                    <measurement group_id="O2" value="5.7" spread="10.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DB Period: Week 72</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="17"/>
                    <count group_id="O2" value="58"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.4" spread="12.9"/>
                    <measurement group_id="O2" value="5.6" spread="11.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DB Period: Week 96</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="14"/>
                    <count group_id="O2" value="52"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.8" spread="10.7"/>
                    <measurement group_id="O2" value="8.1" spread="11.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>OL Period: Week 24</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="51"/>
                    <count group_id="O2" value="91"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.3" spread="13.9"/>
                    <measurement group_id="O2" value="8.3" spread="12.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>OL Period: Week 48</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="44"/>
                    <count group_id="O2" value="88"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.7" spread="13.3"/>
                    <measurement group_id="O2" value="7.6" spread="13.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>OL Period: Week 72</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="41"/>
                    <count group_id="O2" value="76"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.0" spread="15.5"/>
                    <measurement group_id="O2" value="9.2" spread="13.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>OL Period: Week 96</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="36"/>
                    <count group_id="O2" value="73"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.6" spread="16.7"/>
                    <measurement group_id="O2" value="8.0" spread="14.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>OL Period: Week 120</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="22"/>
                    <count group_id="O2" value="28"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.7" spread="15.9"/>
                    <measurement group_id="O2" value="7.2" spread="10.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>OL Period: Week 144</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.6" spread="14.4"/>
                    <measurement group_id="O2" value="5.2" spread="13.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>OL Period: Week 168</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="13"/>
                    <count group_id="O2" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.5" spread="17.9"/>
                    <measurement group_id="O2" value="1.7" spread="14.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>OL Period: Week 192</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                    <count group_id="O2" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.0"/>
                    <measurement group_id="O2" value="-0.3" spread="18.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cognitive Assessment: Change From Baseline in Number of Completed Items Measured by Symbol Digit Modalities Test at Weeks 24, 48, 72, 96, 120, 144, 168 and 192</title>
        <description>SDMT measures the time to pair abstract symbols with specific numbers. It is a simple substitution task that gives the examinee 90 seconds to pair specific numbers with given geometric figures as a measure for screening cognitive impairment. The SDMT score is the number of completed items and ranged from 0 (worst outcome) to 110 (best outcome), where higher score indicated better cognitive function.</description>
        <time_frame>Baseline, DB period: Weeks 24, 48, 72 and 96; OL period: Weeks 24, 48, 72, 96, 120, 144, 168 and 192</time_frame>
        <population>Analysis was performed on efficacy population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo/Teriflunomide</title>
            <description>Participants received Placebo matching to teriflunomide tablet orally once daily for 96 weeks in DB treatment period. After completion of DB period, eligible participants entered in OL period and received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW &gt;40 kg) for first 8 weeks. After 8 weeks if individual predicted PK parameter was &lt;= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW&gt;40 kg) in the OL period for additional 96 weeks (i.e., up to Week 192). If individual predicted PK parameters &gt;95th percentile of adult range then participant received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW &gt;40 kg). The adult range (5th-95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL.</description>
          </group>
          <group group_id="O2">
            <title>Teriflunomide/ Teriflunomide</title>
            <description>Participants received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW &gt;40 kg) orally once daily for 8 weeks. After 8 weeks, based on individual predicted PK parameters, teriflunomide was administered in following manner up to 96 weeks: if predicted PK parameters &lt;= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW &gt;40 kg); or if individual predicted PK parameters &gt;95th percentile of adult range then participants received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW &gt;40 kg). The adult range (5th - 95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL. After completion of DB period, eligible participants entered in OL period and continued receiving teriflunomide at the same dose in the OL period for additional 96 weeks (i.e., up to Week 192).</description>
          </group>
        </group_list>
        <measure>
          <title>Cognitive Assessment: Change From Baseline in Number of Completed Items Measured by Symbol Digit Modalities Test at Weeks 24, 48, 72, 96, 120, 144, 168 and 192</title>
          <description>SDMT measures the time to pair abstract symbols with specific numbers. It is a simple substitution task that gives the examinee 90 seconds to pair specific numbers with given geometric figures as a measure for screening cognitive impairment. The SDMT score is the number of completed items and ranged from 0 (worst outcome) to 110 (best outcome), where higher score indicated better cognitive function.</description>
          <population>Analysis was performed on efficacy population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="51"/>
                <count group_id="O2" value="96"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>DB Period: Week 24</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="40"/>
                    <count group_id="O2" value="85"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.8" spread="11.7"/>
                    <measurement group_id="O2" value="3.6" spread="9.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DB Period: Week 48</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="20"/>
                    <count group_id="O2" value="64"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.3" spread="13.8"/>
                    <measurement group_id="O2" value="4.7" spread="10.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DB Period: Week 72</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="17"/>
                    <count group_id="O2" value="58"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.1" spread="13.4"/>
                    <measurement group_id="O2" value="4.5" spread="11.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DB Period: Week 96</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="14"/>
                    <count group_id="O2" value="52"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.1" spread="11.2"/>
                    <measurement group_id="O2" value="6.9" spread="11.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>OL Period: Week 24</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="51"/>
                    <count group_id="O2" value="91"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.8" spread="13.5"/>
                    <measurement group_id="O2" value="7.1" spread="12.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>OL Period: Week 48</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="44"/>
                    <count group_id="O2" value="88"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.5" spread="12.8"/>
                    <measurement group_id="O2" value="6.4" spread="13.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>OL Period: Week 72</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="41"/>
                    <count group_id="O2" value="76"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.4" spread="15.4"/>
                    <measurement group_id="O2" value="8.1" spread="12.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>OL Period: Week 96</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="36"/>
                    <count group_id="O2" value="73"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.3" spread="16.6"/>
                    <measurement group_id="O2" value="7.6" spread="12.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>OL Period: Week 120</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="22"/>
                    <count group_id="O2" value="28"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.7" spread="14.7"/>
                    <measurement group_id="O2" value="6.3" spread="11.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>OL Period: Week 144</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.8" spread="15.1"/>
                    <measurement group_id="O2" value="3.7" spread="13.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>OL Period: Week 168</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="13"/>
                    <count group_id="O2" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.7" spread="15.5"/>
                    <measurement group_id="O2" value="-0.3" spread="15.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>OL Period: Week 192</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                    <count group_id="O2" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.0"/>
                    <measurement group_id="O2" value="-1.5" spread="18.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cognitive Assessment: Change From Baseline in Brief Visuospatial Memory Test-Revised (BVMT-R) Scores at Weeks 96 and 192</title>
        <description>The BVMT consists of three trials in which participants must recall shapes by drawing figures on a blank page (response booklet) after being given the opportunity to memorize the figures (given in BMVT-R form) for 10 seconds. BMVT-R form consists of six figures. Points are awarded based on the accuracy of the drawn figure and by correct placement on the blank page. A minimum of 0 to 12 points/scores are awarded per trial, so a participant can score between 0 and 36 points for all three trials (by adding the points/score from each trial), where higher score indicates better outcome.</description>
        <time_frame>Baseline, Weeks 96 and 192</time_frame>
        <population>Analysis was performed on efficacy population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo/Teriflunomide</title>
            <description>Participants received Placebo matching to teriflunomide tablet orally once daily for 96 weeks in DB treatment period. After completion of DB period, eligible participants entered in OL period and received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW &gt;40 kg) for first 8 weeks. After 8 weeks if individual predicted PK parameter was &lt;= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW&gt;40 kg) in the OL period for additional 96 weeks (i.e., up to Week 192). If individual predicted PK parameters &gt;95th percentile of adult range then participant received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW &gt;40 kg). The adult range (5th-95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL.</description>
          </group>
          <group group_id="O2">
            <title>Teriflunomide/ Teriflunomide</title>
            <description>Participants received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW &gt;40 kg) orally once daily for 8 weeks. After 8 weeks, based on individual predicted PK parameters, teriflunomide was administered in following manner up to 96 weeks: if predicted PK parameters &lt;= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW &gt;40 kg); or if individual predicted PK parameters &gt;95th percentile of adult range then participants received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW &gt;40 kg). The adult range (5th - 95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL. After completion of DB period, eligible participants entered in OL period and continued receiving teriflunomide at the same dose in the OL period for additional 96 weeks (i.e., up to Week 192).</description>
          </group>
        </group_list>
        <measure>
          <title>Cognitive Assessment: Change From Baseline in Brief Visuospatial Memory Test-Revised (BVMT-R) Scores at Weeks 96 and 192</title>
          <description>The BVMT consists of three trials in which participants must recall shapes by drawing figures on a blank page (response booklet) after being given the opportunity to memorize the figures (given in BMVT-R form) for 10 seconds. BMVT-R form consists of six figures. Points are awarded based on the accuracy of the drawn figure and by correct placement on the blank page. A minimum of 0 to 12 points/scores are awarded per trial, so a participant can score between 0 and 36 points for all three trials (by adding the points/score from each trial), where higher score indicates better outcome.</description>
          <population>Analysis was performed on efficacy population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="31"/>
                <count group_id="O2" value="69"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="31"/>
                    <count group_id="O2" value="69"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23.8" spread="7.2"/>
                    <measurement group_id="O2" value="24.8" spread="6.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 96</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                    <count group_id="O2" value="35"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.8" spread="9.3"/>
                    <measurement group_id="O2" value="1.6" spread="5.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 192</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="16"/>
                    <count group_id="O2" value="45"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.0" spread="6.9"/>
                    <measurement group_id="O2" value="1.2" spread="5.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cognitive Assessment: Change From Baseline in Trail Making Test- Part A (TMT-A) Test Scores (in Seconds) at Week 96 and 192</title>
        <description>'Trail Making Test Part A' is a neuropsychological test of visual attention and task switching. The task requires a participant to 'connect-the-dots' of 25 consecutive numbers (1,2, 3, etc.) in sequential order on a sheet of paper or computer screen. The goal of the participant is to finish the test as quickly as possible, and the time taken to complete the test used as the primary performance metric (in seconds). This is a timed test and the number of seconds to complete the task is recorded. Maximum time allowed is 300 seconds. A lower score indicated better cognitive function.</description>
        <time_frame>Baseline, Weeks 96 and 192</time_frame>
        <population>Analysis was performed on efficacy population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo/Teriflunomide</title>
            <description>Participants received Placebo matching to teriflunomide tablet orally once daily for 96 weeks in DB treatment period. After completion of DB period, eligible participants entered in OL period and received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW &gt;40 kg) for first 8 weeks. After 8 weeks if individual predicted PK parameter was &lt;= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW&gt;40 kg) in the OL period for additional 96 weeks (i.e., up to Week 192). If individual predicted PK parameters &gt;95th percentile of adult range then participant received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW &gt;40 kg). The adult range (5th-95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL.</description>
          </group>
          <group group_id="O2">
            <title>Teriflunomide/ Teriflunomide</title>
            <description>Participants received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW &gt;40 kg) orally once daily for 8 weeks. After 8 weeks, based on individual predicted PK parameters, teriflunomide was administered in following manner up to 96 weeks: if predicted PK parameters &lt;= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW &gt;40 kg); or if individual predicted PK parameters &gt;95th percentile of adult range then participants received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW &gt;40 kg). The adult range (5th - 95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL. After completion of DB period, eligible participants entered in OL period and continued receiving teriflunomide at the same dose in the OL period for additional 96 weeks (i.e., up to Week 192).</description>
          </group>
        </group_list>
        <measure>
          <title>Cognitive Assessment: Change From Baseline in Trail Making Test- Part A (TMT-A) Test Scores (in Seconds) at Week 96 and 192</title>
          <description>'Trail Making Test Part A' is a neuropsychological test of visual attention and task switching. The task requires a participant to 'connect-the-dots' of 25 consecutive numbers (1,2, 3, etc.) in sequential order on a sheet of paper or computer screen. The goal of the participant is to finish the test as quickly as possible, and the time taken to complete the test used as the primary performance metric (in seconds). This is a timed test and the number of seconds to complete the task is recorded. Maximum time allowed is 300 seconds. A lower score indicated better cognitive function.</description>
          <population>Analysis was performed on efficacy population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.</population>
          <units>seconds</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="14"/>
                    <count group_id="O2" value="29"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="43.4" spread="24.2"/>
                    <measurement group_id="O2" value="47.1" spread="23.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 96</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                    <count group_id="O2" value="13"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.4" spread="9.0"/>
                    <measurement group_id="O2" value="-3.1" spread="19.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 192</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.3" spread="20.7"/>
                    <measurement group_id="O2" value="-6.6" spread="17.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cognitive Assessment: Change From Baseline in Trail Making Test B (TMT-B) Test Scores (in Seconds) at Weeks 96 and 192</title>
        <description>TMT-B is a cognitive test that gives a measure of various aspects of cognitive performance. It is used to measure cognitive fatigue. The test consisted of 25 circles containing 13 sequential numbers (1 to 13) and 12 sequential letters (A to L) positioned. The test evaluates the time (in seconds) to correctly order letters and numbers in alternate order (1, A, 2, B etc.). Maximum time allowed is 300 seconds, where less time/lower score indicated better cognitive function/performance.</description>
        <time_frame>Baseline, Weeks 96 and 192</time_frame>
        <population>Analysis was performed on efficacy population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo/Teriflunomide</title>
            <description>Participants received Placebo matching to teriflunomide tablet orally once daily for 96 weeks in DB treatment period. After completion of DB period, eligible participants entered in OL period and received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW &gt;40 kg) for first 8 weeks. After 8 weeks if individual predicted PK parameter was &lt;= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW&gt;40 kg) in the OL period for additional 96 weeks (i.e., up to Week 192). If individual predicted PK parameters &gt;95th percentile of adult range then participant received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW &gt;40 kg). The adult range (5th-95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL.</description>
          </group>
          <group group_id="O2">
            <title>Teriflunomide/ Teriflunomide</title>
            <description>Participants received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW &gt;40 kg) orally once daily for 8 weeks. After 8 weeks, based on individual predicted PK parameters, teriflunomide was administered in following manner up to 96 weeks: if predicted PK parameters &lt;= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW &gt;40 kg); or if individual predicted PK parameters &gt;95th percentile of adult range then participants received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW &gt;40 kg). The adult range (5th - 95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL. After completion of DB period, eligible participants entered in OL period and continued receiving teriflunomide at the same dose in the OL period for additional 96 weeks (i.e., up to Week 192).</description>
          </group>
        </group_list>
        <measure>
          <title>Cognitive Assessment: Change From Baseline in Trail Making Test B (TMT-B) Test Scores (in Seconds) at Weeks 96 and 192</title>
          <description>TMT-B is a cognitive test that gives a measure of various aspects of cognitive performance. It is used to measure cognitive fatigue. The test consisted of 25 circles containing 13 sequential numbers (1 to 13) and 12 sequential letters (A to L) positioned. The test evaluates the time (in seconds) to correctly order letters and numbers in alternate order (1, A, 2, B etc.). Maximum time allowed is 300 seconds, where less time/lower score indicated better cognitive function/performance.</description>
          <population>Analysis was performed on efficacy population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.</population>
          <units>seconds</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="14"/>
                    <count group_id="O2" value="28"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="113.8" spread="81.5"/>
                    <measurement group_id="O2" value="115.0" spread="44.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 96</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                    <count group_id="O2" value="13"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-19.8" spread="33.7"/>
                    <measurement group_id="O2" value="-29.5" spread="56.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 192</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-37.0" spread="83.3"/>
                    <measurement group_id="O2" value="-18.8" spread="37.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cognitive Assessment: Change From Baseline in Beery Visual-motor Integration (BVMI) Scores at Weeks 96 and 192</title>
        <description>The Beery VMI is a non-verbal assessment that assessed the extent to which individuals can integrate their visual and motor abilities. The participants were provided with geometric designs ranging from simple line drawings to more complex figures and were asked to copy the designs. The test consisted of 24 figures. One point was scored for each successful copy of drawings and no scoring was given when the participant failed to copy the drawings properly. Each successful copying of drawings was summed up and the total was scored on a scale ranged from 0 to 24, where higher score indicated better visual construction skills/better visual and motor abilities and lower score indicated poor visual construction skills/poor visual and motor abilities.</description>
        <time_frame>Baseline, Weeks 96 and 192</time_frame>
        <population>Analysis was performed on efficacy population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo/Teriflunomide</title>
            <description>Participants received Placebo matching to teriflunomide tablet orally once daily for 96 weeks in DB treatment period. After completion of DB period, eligible participants entered in OL period and received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW &gt;40 kg) for first 8 weeks. After 8 weeks if individual predicted PK parameter was &lt;= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW&gt;40 kg) in the OL period for additional 96 weeks (i.e., up to Week 192). If individual predicted PK parameters &gt;95th percentile of adult range then participant received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW &gt;40 kg). The adult range (5th-95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL.</description>
          </group>
          <group group_id="O2">
            <title>Teriflunomide/ Teriflunomide</title>
            <description>Participants received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW &gt;40 kg) orally once daily for 8 weeks. After 8 weeks, based on individual predicted PK parameters, teriflunomide was administered in following manner up to 96 weeks: if predicted PK parameters &lt;= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW &gt;40 kg); or if individual predicted PK parameters &gt;95th percentile of adult range then participants received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW &gt;40 kg). The adult range (5th - 95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL. After completion of DB period, eligible participants entered in OL period and continued receiving teriflunomide at the same dose in the OL period for additional 96 weeks (i.e., up to Week 192).</description>
          </group>
        </group_list>
        <measure>
          <title>Cognitive Assessment: Change From Baseline in Beery Visual-motor Integration (BVMI) Scores at Weeks 96 and 192</title>
          <description>The Beery VMI is a non-verbal assessment that assessed the extent to which individuals can integrate their visual and motor abilities. The participants were provided with geometric designs ranging from simple line drawings to more complex figures and were asked to copy the designs. The test consisted of 24 figures. One point was scored for each successful copy of drawings and no scoring was given when the participant failed to copy the drawings properly. Each successful copying of drawings was summed up and the total was scored on a scale ranged from 0 to 24, where higher score indicated better visual construction skills/better visual and motor abilities and lower score indicated poor visual construction skills/poor visual and motor abilities.</description>
          <population>Analysis was performed on efficacy population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="39"/>
                <count group_id="O2" value="82"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="39"/>
                    <count group_id="O2" value="82"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="26.1" spread="5.2"/>
                    <measurement group_id="O2" value="25.9" spread="4.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 96</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                    <count group_id="O2" value="47"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.6" spread="2.4"/>
                    <measurement group_id="O2" value="-0.4" spread="4.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 192</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="26"/>
                    <count group_id="O2" value="58"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.1" spread="5.4"/>
                    <measurement group_id="O2" value="0.4" spread="2.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cognitive Assessment: Change From Baseline in Wechsler Abbreviated Scale of Intelligence-II (WASI-II) Vocabulary Total Raw Scores at Weeks 96 and 192</title>
        <description>The WASI-II: Vocabulary test is a quick estimate of an individual's level of intellectual functioning which comprised of 31 total items that required the participant to orally define 3 images and 28 words presented both orally and visually. Items 1 to 3 rated on a score of 0 or 1, items 4 and 5 rated on a score of 0 or 2, items 6 to 31 rated on a scale of 0 to 2. Each item score was summed up to derive the total score which ranged from 0 (minimum score) to 59 (maximum score), where higher score indicated better level of intellectual functioning/higher level of intelligence.</description>
        <time_frame>Baseline, Weeks 96 and 192</time_frame>
        <population>Analysis was performed on efficacy population. Here, &quot;overall number of participants analyzed&quot; = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo/Teriflunomide</title>
            <description>Participants received Placebo matching to teriflunomide tablet orally once daily for 96 weeks in DB treatment period. After completion of DB period, eligible participants entered in OL period and received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW &gt;40 kg) for first 8 weeks. After 8 weeks if individual predicted PK parameter was &lt;= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW&gt;40 kg) in the OL period for additional 96 weeks (i.e., up to Week 192). If individual predicted PK parameters &gt;95th percentile of adult range then participant received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW &gt;40 kg). The adult range (5th-95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL.</description>
          </group>
          <group group_id="O2">
            <title>Teriflunomide/ Teriflunomide</title>
            <description>Participants received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW &gt;40 kg) orally once daily for 8 weeks. After 8 weeks, based on individual predicted PK parameters, teriflunomide was administered in following manner up to 96 weeks: if predicted PK parameters &lt;= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW &gt;40 kg); or if individual predicted PK parameters &gt;95th percentile of adult range then participants received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW &gt;40 kg). The adult range (5th - 95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL. After completion of DB period, eligible participants entered in OL period and continued receiving teriflunomide at the same dose in the OL period for additional 96 weeks (i.e., up to Week 192).</description>
          </group>
        </group_list>
        <measure>
          <title>Cognitive Assessment: Change From Baseline in Wechsler Abbreviated Scale of Intelligence-II (WASI-II) Vocabulary Total Raw Scores at Weeks 96 and 192</title>
          <description>The WASI-II: Vocabulary test is a quick estimate of an individual's level of intellectual functioning which comprised of 31 total items that required the participant to orally define 3 images and 28 words presented both orally and visually. Items 1 to 3 rated on a score of 0 or 1, items 4 and 5 rated on a score of 0 or 2, items 6 to 31 rated on a scale of 0 to 2. Each item score was summed up to derive the total score which ranged from 0 (minimum score) to 59 (maximum score), where higher score indicated better level of intellectual functioning/higher level of intelligence.</description>
          <population>Analysis was performed on efficacy population. Here, &quot;overall number of participants analyzed&quot; = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
                <count group_id="O2" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                    <count group_id="O2" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="39.0"/>
                    <measurement group_id="O2" value="34.3" spread="7.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 96</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                    <count group_id="O2" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.0"/>
                    <measurement group_id="O2" value="4.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 192</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                    <count group_id="O2" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.0"/>
                    <measurement group_id="O2" value="5.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cognitive Assessment: Change From Baseline in Delis-Kaplan Executive Function System (D-KEFS) Letter Fluency Total Correct Raw Score at Weeks 96 and 192</title>
        <description>Letter Fluency is a condition measured in the D-KEFS. Participants were asked to name as many words as they can, starting with a specified letter for 60 seconds. The words cannot be names, places, numbers or grammatical variants of previous answers. Repeated answers were not scored as a correct response. There were 3 trials, with 3 different letters. The total number of correct responses was totaled for all 3 trials and a letter fluency score was given. A higher score was considered better. There was no set range as the score depends on how many correct words the participant relays in the given time period.</description>
        <time_frame>Baseline, Weeks 96 and 192</time_frame>
        <population>Analysis was performed on efficacy population. Here, &quot;overall number of participants analyzed&quot; = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo/Teriflunomide</title>
            <description>Participants received Placebo matching to teriflunomide tablet orally once daily for 96 weeks in DB treatment period. After completion of DB period, eligible participants entered in OL period and received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW &gt;40 kg) for first 8 weeks. After 8 weeks if individual predicted PK parameter was &lt;= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW&gt;40 kg) in the OL period for additional 96 weeks (i.e., up to Week 192). If individual predicted PK parameters &gt;95th percentile of adult range then participant received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW &gt;40 kg). The adult range (5th-95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL.</description>
          </group>
          <group group_id="O2">
            <title>Teriflunomide/ Teriflunomide</title>
            <description>Participants received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW &gt;40 kg) orally once daily for 8 weeks. After 8 weeks, based on individual predicted PK parameters, teriflunomide was administered in following manner up to 96 weeks: if predicted PK parameters &lt;= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW &gt;40 kg); or if individual predicted PK parameters &gt;95th percentile of adult range then participants received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW &gt;40 kg). The adult range (5th - 95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL. After completion of DB period, eligible participants entered in OL period and continued receiving teriflunomide at the same dose in the OL period for additional 96 weeks (i.e., up to Week 192).</description>
          </group>
        </group_list>
        <measure>
          <title>Cognitive Assessment: Change From Baseline in Delis-Kaplan Executive Function System (D-KEFS) Letter Fluency Total Correct Raw Score at Weeks 96 and 192</title>
          <description>Letter Fluency is a condition measured in the D-KEFS. Participants were asked to name as many words as they can, starting with a specified letter for 60 seconds. The words cannot be names, places, numbers or grammatical variants of previous answers. Repeated answers were not scored as a correct response. There were 3 trials, with 3 different letters. The total number of correct responses was totaled for all 3 trials and a letter fluency score was given. A higher score was considered better. There was no set range as the score depends on how many correct words the participant relays in the given time period.</description>
          <population>Analysis was performed on efficacy population. Here, &quot;overall number of participants analyzed&quot; = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="2"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="32.5" spread="3.5"/>
                    <measurement group_id="O2" value="21.0" spread="6.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 96</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                    <count group_id="O2" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.0"/>
                    <measurement group_id="O2" value="4.0" spread="9.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 192</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                    <count group_id="O2" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.0"/>
                    <measurement group_id="O2" value="-6.5" spread="16.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cognitive Assessment: Change From Baseline in Delis-Kaplan Executive Function System Category Fluency Total Correct Raw Score at Weeks 96 and 192</title>
        <description>Category Fluency is a condition measured in the D-KEFS. It measured participant's ability to generate words from three different categories (e.g., fruits, vegetables and animals), within a minute for each category. Total score was number of correct words for each category with no points for repetitions or non-words. Score ranged from 0 to unlimited, where 0 = low score, higher score indicated better performance.</description>
        <time_frame>Baseline, Weeks 96 and 192</time_frame>
        <population>Analysis was performed on efficacy population. Here, &quot;overall number of participants analyzed&quot; = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo/Teriflunomide</title>
            <description>Participants received Placebo matching to teriflunomide tablet orally once daily for 96 weeks in DB treatment period. After completion of DB period, eligible participants entered in OL period and received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW &gt;40 kg) for first 8 weeks. After 8 weeks if individual predicted PK parameter was &lt;= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW&gt;40 kg) in the OL period for additional 96 weeks (i.e., up to Week 192). If individual predicted PK parameters &gt;95th percentile of adult range then participant received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW &gt;40 kg). The adult range (5th-95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL.</description>
          </group>
          <group group_id="O2">
            <title>Teriflunomide/ Teriflunomide</title>
            <description>Participants received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW &gt;40 kg) orally once daily for 8 weeks. After 8 weeks, based on individual predicted PK parameters, teriflunomide was administered in following manner up to 96 weeks: if predicted PK parameters &lt;= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW &gt;40 kg); or if individual predicted PK parameters &gt;95th percentile of adult range then participants received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW &gt;40 kg). The adult range (5th - 95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL. After completion of DB period, eligible participants entered in OL period and continued receiving teriflunomide at the same dose in the OL period for additional 96 weeks (i.e., up to Week 192).</description>
          </group>
        </group_list>
        <measure>
          <title>Cognitive Assessment: Change From Baseline in Delis-Kaplan Executive Function System Category Fluency Total Correct Raw Score at Weeks 96 and 192</title>
          <description>Category Fluency is a condition measured in the D-KEFS. It measured participant's ability to generate words from three different categories (e.g., fruits, vegetables and animals), within a minute for each category. Total score was number of correct words for each category with no points for repetitions or non-words. Score ranged from 0 to unlimited, where 0 = low score, higher score indicated better performance.</description>
          <population>Analysis was performed on efficacy population. Here, &quot;overall number of participants analyzed&quot; = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="2"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="28.0" spread="1.4"/>
                    <measurement group_id="O2" value="27.5" spread="9.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 96</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                    <count group_id="O2" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.0"/>
                    <measurement group_id="O2" value="5.0" spread="5.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 192</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                    <count group_id="O2" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.0"/>
                    <measurement group_id="O2" value="-13.5" spread="17.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cognitive Assessment - Selective Reminding Test (SRT): Change From Baseline in Total Number of Words on Delayed Recall at Weeks 96 and 192</title>
        <description>SRT is a test to assess verbal learning and memory. During the administration of the SRT only the examiner and the participant should be in the testing room. A list of twelve words was read aloud by the examiner at a rate of one word per two seconds. The participant is asked to recall all twelve words after a 30 minute delay. Only the words that were missed on the preceding trial were given in the consecutive trial. The total score represented a sum score of total 6 trials, therefore the score range was from 0 to 72. The lower the score the worse the outcome, higher score indicated better recall.</description>
        <time_frame>Baseline, Weeks 96 and 192</time_frame>
        <population>Analysis was performed on efficacy population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo/Teriflunomide</title>
            <description>Participants received Placebo matching to teriflunomide tablet orally once daily for 96 weeks in DB treatment period. After completion of DB period, eligible participants entered in OL period and received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW &gt;40 kg) for first 8 weeks. After 8 weeks if individual predicted PK parameter was &lt;= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW&gt;40 kg) in the OL period for additional 96 weeks (i.e., up to Week 192). If individual predicted PK parameters &gt;95th percentile of adult range then participant received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW &gt;40 kg). The adult range (5th-95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL.</description>
          </group>
          <group group_id="O2">
            <title>Teriflunomide/ Teriflunomide</title>
            <description>Participants received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW &gt;40 kg) orally once daily for 8 weeks. After 8 weeks, based on individual predicted PK parameters, teriflunomide was administered in following manner up to 96 weeks: if predicted PK parameters &lt;= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW &gt;40 kg); or if individual predicted PK parameters &gt;95th percentile of adult range then participants received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW &gt;40 kg). The adult range (5th - 95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL. After completion of DB period, eligible participants entered in OL period and continued receiving teriflunomide at the same dose in the OL period for additional 96 weeks (i.e., up to Week 192).</description>
          </group>
        </group_list>
        <measure>
          <title>Cognitive Assessment - Selective Reminding Test (SRT): Change From Baseline in Total Number of Words on Delayed Recall at Weeks 96 and 192</title>
          <description>SRT is a test to assess verbal learning and memory. During the administration of the SRT only the examiner and the participant should be in the testing room. A list of twelve words was read aloud by the examiner at a rate of one word per two seconds. The participant is asked to recall all twelve words after a 30 minute delay. Only the words that were missed on the preceding trial were given in the consecutive trial. The total score represented a sum score of total 6 trials, therefore the score range was from 0 to 72. The lower the score the worse the outcome, higher score indicated better recall.</description>
          <population>Analysis was performed on efficacy population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
                <count group_id="O2" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="2"/>
                    <count group_id="O2" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.5" spread="4.9"/>
                    <measurement group_id="O2" value="10.0" spread="1.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 96</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                    <count group_id="O2" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.0"/>
                    <measurement group_id="O2" value="-0.5" spread="2.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 192</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                    <count group_id="O2" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0"/>
                    <measurement group_id="O2" value="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>DB: Pharmacokinetics: Steady-state Trough Concentration (Ctrough) of Teriflunomide</title>
        <description>Ctrough was defined as the concentration reached by the drug before the next dose administered. Data for this outcome measure was planned to be collected and analyzed separately for each dose of Teriflunomide. PK samples for teriflunomide 3.5 mg were collected during the first 8 weeks but all participants were switched to teriflunomide 7 mg after Week 8. Hence, plasma concentration of teriflunomide 7 mg and 14 mg were reported.</description>
        <time_frame>Predose on Week 36</time_frame>
        <population>Analysis was performed on PK population which included all randomized participants exposed to DB study medication and had at least 1 PK sample taken. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and &quot;0'' signifies that none of the participant was evaluable for Teriflunomide 3.5 mg arm.</population>
        <group_list>
          <group group_id="O1">
            <title>Teriflunomide 3.5 mg</title>
            <description>Participants with BW up to 40 kg received 1 teriflunomide tablet, 3.5 mg orally once daily for 8 weeks. After 8 weeks, based on individual predicted PK parameters, teriflunomide was administered in following manner up to 96 weeks: if predicted PK parameters &lt;= 95th percentile of adult range then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW &gt;40 kg); or if predicted PK parameters &gt;95th percentile of adult range then participants received 1 tablet of 3.5 mg teriflunomide daily (for BW &lt;= 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW &gt;40 kg).</description>
          </group>
          <group group_id="O2">
            <title>Teriflunomide 7 mg</title>
            <description>Participants with BW &gt;40 kg received 1 teriflunomide tablet, 7 mg orally once daily for 8 weeks. After 8 weeks, based on individual predicted PK parameters, teriflunomide was administered in following manner up to 96 weeks: if predicted PK parameters &lt;= 95th percentile of adult range after 7 mg once daily then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW &gt;40 kg); or if predicted PK parameters &gt;95th percentile of adult range then participants received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW &gt;40 kg).</description>
          </group>
          <group group_id="O3">
            <title>Teriflunomide 14 mg</title>
            <description>After 8 weeks, based on individual predicted PK parameters, teriflunomide was administered in following manner up to 96 weeks: if predicted PK parameters &lt;= 95th percentile of adult range after 7 mg once daily then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW &gt;40 kg); or if predicted PK parameters &gt;95th percentile of adult range then participants received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW &gt;40 kg).</description>
          </group>
        </group_list>
        <measure>
          <title>DB: Pharmacokinetics: Steady-state Trough Concentration (Ctrough) of Teriflunomide</title>
          <description>Ctrough was defined as the concentration reached by the drug before the next dose administered. Data for this outcome measure was planned to be collected and analyzed separately for each dose of Teriflunomide. PK samples for teriflunomide 3.5 mg were collected during the first 8 weeks but all participants were switched to teriflunomide 7 mg after Week 8. Hence, plasma concentration of teriflunomide 7 mg and 14 mg were reported.</description>
          <population>Analysis was performed on PK population which included all randomized participants exposed to DB study medication and had at least 1 PK sample taken. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and &quot;0'' signifies that none of the participant was evaluable for Teriflunomide 3.5 mg arm.</population>
          <units>micrograms per milliliter</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="10"/>
                <count group_id="O3" value="66"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="53.1" spread="25.3"/>
                    <measurement group_id="O3" value="67.8" spread="41.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>OL: Time to First Confirmed Clinical Relapse</title>
        <description>Time to first clinical relapse was defined as duration (in weeks) after enrollment in OL period and first confirmed clinical relapse. Clinical relapses were defined as new or recurrent neurological symptoms not associated with fever or infection, lasted at least 24 hours and accompanied by new objective neurological findings upon neurological examination and documented by standardized, quantified FSSs which included 8 items and items were rated on different scales: brain stem, cerebellar &amp; cerebral functions rated on scale of 0 to 5; visual, pyramidal, sensory and bowel/bladder rated on scale of 0 to 6 and ambulation on scale of 0 to 12 where higher score in each scale indicated worsened neurological function. Confirmed clinical relapse were reviewed and confirmed by independent RAP. Participant without confirmed clinical relapse, was considered as clinical relapse free until end of Week 192.</description>
        <time_frame>Baseline up to Week 192</time_frame>
        <population>Analysis was performed on efficacy population.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo/Teriflunomide</title>
            <description>Participants received Placebo matching to teriflunomide tablet orally once daily for 96 weeks in DB treatment period. After completion of DB period, eligible participants entered in OL period and received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW &gt;40 kg) for first 8 weeks. After 8 weeks if individual predicted PK parameter was &lt;= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW&gt;40 kg) in the OL period for additional 96 weeks (i.e., up to Week 192). If individual predicted PK parameters &gt;95th percentile of adult range then participant received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW &gt;40 kg). The adult range (5th-95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL.</description>
          </group>
          <group group_id="O2">
            <title>Teriflunomide/ Teriflunomide</title>
            <description>Participants received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW &gt;40 kg) orally once daily for 8 weeks. After 8 weeks, based on individual predicted PK parameters, teriflunomide was administered in following manner up to 96 weeks: if predicted PK parameters &lt;= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW &gt;40 kg); or if individual predicted PK parameters &gt;95th percentile of adult range then participants received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW &gt;40 kg). The adult range (5th - 95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL. After completion of DB period, eligible participants entered in OL period and continued receiving teriflunomide at the same dose in the OL period for additional 96 weeks (i.e., up to Week 192).</description>
          </group>
        </group_list>
        <measure>
          <title>OL: Time to First Confirmed Clinical Relapse</title>
          <description>Time to first clinical relapse was defined as duration (in weeks) after enrollment in OL period and first confirmed clinical relapse. Clinical relapses were defined as new or recurrent neurological symptoms not associated with fever or infection, lasted at least 24 hours and accompanied by new objective neurological findings upon neurological examination and documented by standardized, quantified FSSs which included 8 items and items were rated on different scales: brain stem, cerebellar &amp; cerebral functions rated on scale of 0 to 5; visual, pyramidal, sensory and bowel/bladder rated on scale of 0 to 6 and ambulation on scale of 0 to 12 where higher score in each scale indicated worsened neurological function. Confirmed clinical relapse were reviewed and confirmed by independent RAP. Participant without confirmed clinical relapse, was considered as clinical relapse free until end of Week 192.</description>
          <population>Analysis was performed on efficacy population.</population>
          <units>weeks</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="52"/>
                <count group_id="O2" value="100"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="95.86" lower_limit="0.6" upper_limit="176.0"/>
                    <measurement group_id="O2" value="96.00" lower_limit="1.0" upper_limit="183.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.693</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.37</ci_lower_limit>
            <ci_upper_limit>1.296</ci_upper_limit>
            <estimate_desc>Hazard ratio estimated using a Cox proportional-hazards model using treatment group, region, pubertal status, age, and number of relapses in the year prior to randomisation as covariates and with robust variance estimation.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>OL: Pharmacokinetics: Steady-state Trough Concentration (Ctrough) of Teriflunomide</title>
        <description>Ctrough was defined as the concentration reached by the drug before the next dose is administered. Data for this outcome measure was planned to be collected and analyzed separately for each dose of teriflunomide. PK samples for teriflunomide 3.5 mg were collected during the first 8 weeks but all participants were switched to teriflunomide 7 mg after Week 8. Hence, plasma concentration of teriflunomide 7 mg and 14 mg were reported.</description>
        <time_frame>Pre-dose at Week 36</time_frame>
        <population>Analysis was performed on PK population which included all randomized participants exposed to study medication, regardless of the amount of treatment administered who had at least one PK sample taken in OL period. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and &quot;0'' signifies that none of the participant was evaluable for Placebo/Teriflunomide 3.5 mg and Teriflunomide/Teriflunomide 3.5 mg arms.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo / Teriflunomide 3.5 mg</title>
            <description>Participants previously treated with placebo in DB period received 1 teriflunomide tablet 3.5 mg orally once daily for first 8 weeks of OL period. After 8 weeks, based on individual predicted PK parameters, teriflunomide was administered in following manner up to Week 192: if predicted PK parameters &lt;= 95th percentile of adult range then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW &gt;40 kg); or if predicted PK parameters &gt;95th percentile of adult range then participants received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW &gt;40 kg).</description>
          </group>
          <group group_id="O2">
            <title>Placebo / Teriflunomide 7 mg</title>
            <description>Participants previously treated with placebo during the DB period received teriflunomide 7 mg for 96 weeks in the OL period (i.e., up to Week 192).</description>
          </group>
          <group group_id="O3">
            <title>Placebo / Teriflunomide 14 mg</title>
            <description>Participants previously treated with placebo during the DB period received teriflunomide 14 mg for 96 weeks in OL period (i.e., up to Week 192).</description>
          </group>
          <group group_id="O4">
            <title>Teriflunomide / Teriflunomide 3.5 mg</title>
            <description>Participants previously treated with teriflunomide during the DB period received 1 teriflunomide tablet 3.5 mg orally once daily for first 8 weeks of OL period. After 8 weeks, based on individual predicted PK parameters, teriflunomide was administered in following manner up to Week 192: if predicted PK parameters &lt;= 95th percentile of adult range then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW &gt;40 kg); or if predicted PK parameters &gt;95th percentile of adult range then participants received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW &gt;40 kg).</description>
          </group>
          <group group_id="O5">
            <title>Teriflunomide / Teriflunomide 7 mg</title>
            <description>Participants previously treated with teriflunomide 7 mg during DB period continued receiving teriflunomide 7mg in the OL period for additional 96 weeks (i.e., up to Week 192).</description>
          </group>
          <group group_id="O6">
            <title>Teriflunomide / Teriflunomide 14 mg</title>
            <description>Participants previously treated with teriflunomide 14 mg during DB period continued receiving teriflunomide 14mg in the OL period for additional 96 weeks (i.e., up to Week 192).</description>
          </group>
        </group_list>
        <measure>
          <title>OL: Pharmacokinetics: Steady-state Trough Concentration (Ctrough) of Teriflunomide</title>
          <description>Ctrough was defined as the concentration reached by the drug before the next dose is administered. Data for this outcome measure was planned to be collected and analyzed separately for each dose of teriflunomide. PK samples for teriflunomide 3.5 mg were collected during the first 8 weeks but all participants were switched to teriflunomide 7 mg after Week 8. Hence, plasma concentration of teriflunomide 7 mg and 14 mg were reported.</description>
          <population>Analysis was performed on PK population which included all randomized participants exposed to study medication, regardless of the amount of treatment administered who had at least one PK sample taken in OL period. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and &quot;0'' signifies that none of the participant was evaluable for Placebo/Teriflunomide 3.5 mg and Teriflunomide/Teriflunomide 3.5 mg arms.</population>
          <units>micrograms per milliliter</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="12"/>
                <count group_id="O3" value="31"/>
                <count group_id="O4" value="0"/>
                <count group_id="O5" value="2"/>
                <count group_id="O6" value="79"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="45.8" spread="35.3"/>
                    <measurement group_id="O3" value="50.4" spread="23.8"/>
                    <measurement group_id="O5" value="33.7" spread="10.7"/>
                    <measurement group_id="O6" value="63.6" spread="35.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events (AEs) were collected from first dose of study drug up to 96 weeks (for DB period arms) and from first dose of study drug in OL period up to Week 192 (for OL period arms).</time_frame>
      <desc>Reported AEs were treatment-emergent AEs (TEAEs), which developed/worsened during TEAE period (defined as time from first intake of investigational medicinal product [IMP] in DB period up to last intake of IMP in OL period). Safety population included all randomized participants exposed to study medication, regardless of the amount of treatment administered.</desc>
      <group_list>
        <group group_id="E1">
          <title>Double-Blind Treatment Period: Placebo</title>
          <description>Participants received placebo matching to teriflunomide tablet orally once daily for 96 weeks.</description>
        </group>
        <group group_id="E2">
          <title>Double-Blind Treatment Period: Teriflunomide</title>
          <description>Participants received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW &gt;40kg) orally once daily for 8 weeks. After 8 weeks, based on individual predicted PK parameters, teriflunomide was administered in following manner up to 96 weeks: if predicted PK parameters &lt;=95th percentile of adult range after 7 mg once daily then, participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW&gt;40kg); or if individual predicted PK parameters &gt;95th percentile of adult range then participants received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40kg) or 1 tablet of 7 mg teriflunomide daily (for BW&gt;40 kg). The adult range (5th-95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL.</description>
        </group>
        <group group_id="E3">
          <title>Open-Label Treatment Period: Placebo/Teriflunomide</title>
          <description>Participants received Placebo matching to teriflunomide tablet orally once daily for 96 weeks in DB treatment period. After completion of DB period, eligible participants entered in OL period and received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (BW &gt;40 kg) for first 8 weeks. After 8 weeks if individual predicted PK parameter was &lt;= 95th percentile of adult range at 7 mg once daily, then participants received 7 mg teriflunomide (for BW up to 40 kg) or 14 mg teriflunomide (for BW&gt;40 kg) in the OL period for additional 96 weeks (i.e., up to Week 192). If individual predicted PK parameters &gt;95th percentile of adult range then participant received 3.5 mg teriflunomide daily (for BW up to 40 kg) or 7 mg teriflunomide daily (for BW &gt;40 kg). The adult range (5th-95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL.</description>
        </group>
        <group group_id="E4">
          <title>Open-Label Treatment Period: Teriflunomide/ Teriflunomide</title>
          <description>Participants previously treated with Teriflunomide during DB period continued receiving Teriflunomide at the same dose in the OL period for additional 96 weeks (i.e., up to Week 192).</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDra 24.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="109"/>
                <counts group_id="E3" subjects_affected="15" subjects_at_risk="52"/>
                <counts group_id="E4" subjects_affected="14" subjects_at_risk="100"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="109"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="100"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Cardiomyopathy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="109"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="100"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Congenital, familial and genetic disorders</title>
            <event_list>
              <event>
                <sub_title>Familial Mediterranean Fever</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="100"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Diplopia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="109"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="100"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Anal Fissure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Anal Fistula</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="109"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Food Poisoning</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Pancreatic Disorder</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Pancreatitis Acute</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="109"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="100"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Gait Disturbance</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="100"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Hepatic Function Abnormal</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="100"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Acute Sinusitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Appendicitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Coronavirus Infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Encephalitis Viral</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Pulmonary Tuberculosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="109"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Tonsillitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Upper Respiratory Tract Infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="109"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="100"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Intentional Overdose</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Joint Dislocation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Lumbar Vertebral Fracture</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="109"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Peripheral Nerve Injury</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="109"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Skin Laceration</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="100"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine Aminotransferase Increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="109"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="52"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Blood Creatine Phosphokinase Increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="109"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Transaminases Increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="109"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="100"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Epilepsy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="109"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Hypoaesthesia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Multiple Sclerosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="109"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Uhthoff's Phenomenon</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="100"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Pregnancy, puerperium and perinatal conditions</title>
            <event_list>
              <event>
                <sub_title>Pregnancy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="100"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Adjustment Disorder</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Depression Suicidal</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Emotional Disorder Of Childhood</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Suicide Attempt</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="100"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Asthma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="52"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="100"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Drug Eruption</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="100"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>2</frequency_threshold>
        <default_vocab>MedDra 24.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="41" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="89" subjects_at_risk="109"/>
                <counts group_id="E3" subjects_affected="40" subjects_at_risk="52"/>
                <counts group_id="E4" subjects_affected="72" subjects_at_risk="100"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="109"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E4" events="6" subjects_affected="6" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" events="5" subjects_affected="3" subjects_at_risk="109"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="100"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Palpitations</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="109"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="100"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Ear Pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="57"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="109"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Tinnitus</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="109"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="100"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Autoimmune Thyroiditis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="57"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="109"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="100"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Eye Pain</sub_title>
                <counts group_id="E1" events="8" subjects_affected="4" subjects_at_risk="57"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="109"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E4" events="3" subjects_affected="3" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Vision Blurred</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="57"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="109"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E4" events="3" subjects_affected="3" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Visual Impairment</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="57"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="52"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="100"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal Pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" events="13" subjects_affected="11" subjects_at_risk="109"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="52"/>
                <counts group_id="E4" events="11" subjects_affected="8" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Abdominal Pain Upper</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="57"/>
                <counts group_id="E2" events="9" subjects_affected="6" subjects_at_risk="109"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E4" events="4" subjects_affected="3" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Aphthous Ulcer</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="109"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="52"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="109"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="52"/>
                <counts group_id="E4" events="3" subjects_affected="3" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="57"/>
                <counts group_id="E2" events="9" subjects_affected="8" subjects_at_risk="109"/>
                <counts group_id="E3" events="8" subjects_affected="6" subjects_at_risk="52"/>
                <counts group_id="E4" events="9" subjects_affected="7" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Mouth Ulceration</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="109"/>
                <counts group_id="E3" events="4" subjects_affected="2" subjects_at_risk="52"/>
                <counts group_id="E4" events="3" subjects_affected="2" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="57"/>
                <counts group_id="E2" events="12" subjects_affected="10" subjects_at_risk="109"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="52"/>
                <counts group_id="E4" events="4" subjects_affected="4" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="57"/>
                <counts group_id="E2" events="7" subjects_affected="6" subjects_at_risk="109"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="52"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="100"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="109"/>
                <counts group_id="E3" events="4" subjects_affected="2" subjects_at_risk="52"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="5" subjects_affected="3" subjects_at_risk="57"/>
                <counts group_id="E2" events="6" subjects_affected="4" subjects_at_risk="109"/>
                <counts group_id="E3" events="7" subjects_affected="4" subjects_at_risk="52"/>
                <counts group_id="E4" events="4" subjects_affected="4" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Influenza Like Illness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="109"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Non-Cardiac Chest Pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="109"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="57"/>
                <counts group_id="E2" events="8" subjects_affected="5" subjects_at_risk="109"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E4" events="3" subjects_affected="3" subjects_at_risk="100"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Acute Sinusitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="52"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="109"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="52"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Cystitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="109"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="52"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="57"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="109"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="52"/>
                <counts group_id="E4" events="6" subjects_affected="5" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="57"/>
                <counts group_id="E2" events="16" subjects_affected="10" subjects_at_risk="109"/>
                <counts group_id="E3" events="6" subjects_affected="5" subjects_at_risk="52"/>
                <counts group_id="E4" events="6" subjects_affected="5" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" events="6" subjects_affected="5" subjects_at_risk="57"/>
                <counts group_id="E2" events="50" subjects_affected="28" subjects_at_risk="109"/>
                <counts group_id="E3" events="13" subjects_affected="8" subjects_at_risk="52"/>
                <counts group_id="E4" events="37" subjects_affected="20" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Pharyngitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" events="8" subjects_affected="7" subjects_at_risk="109"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E4" events="8" subjects_affected="4" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Respiratory Tract Infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="109"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E4" events="5" subjects_affected="5" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Respiratory Tract Infection Viral</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" events="7" subjects_affected="4" subjects_at_risk="109"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Rhinitis</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="57"/>
                <counts group_id="E2" events="8" subjects_affected="4" subjects_at_risk="109"/>
                <counts group_id="E3" events="4" subjects_affected="2" subjects_at_risk="52"/>
                <counts group_id="E4" events="7" subjects_affected="6" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="57"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="109"/>
                <counts group_id="E3" events="3" subjects_affected="2" subjects_at_risk="52"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Tinea Versicolour</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="57"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="109"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Tonsillitis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="57"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="109"/>
                <counts group_id="E3" events="4" subjects_affected="2" subjects_at_risk="52"/>
                <counts group_id="E4" events="5" subjects_affected="4" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Tracheitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="52"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Tracheobronchitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="52"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Upper Respiratory Tract Infection</sub_title>
                <counts group_id="E1" events="23" subjects_affected="6" subjects_at_risk="57"/>
                <counts group_id="E2" events="66" subjects_affected="24" subjects_at_risk="109"/>
                <counts group_id="E3" events="32" subjects_affected="7" subjects_at_risk="52"/>
                <counts group_id="E4" events="59" subjects_affected="22" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Urinary Tract Infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="109"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="52"/>
                <counts group_id="E4" events="5" subjects_affected="5" subjects_at_risk="100"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Accidental Overdose</sub_title>
                <counts group_id="E1" events="7" subjects_affected="4" subjects_at_risk="57"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="109"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="52"/>
                <counts group_id="E4" events="12" subjects_affected="10" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="109"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="57"/>
                <counts group_id="E2" events="8" subjects_affected="6" subjects_at_risk="109"/>
                <counts group_id="E3" events="3" subjects_affected="2" subjects_at_risk="52"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Ligament Sprain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="57"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="109"/>
                <counts group_id="E3" events="3" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Thermal Burn</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="109"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="52"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="100"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine Aminotransferase Increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="109"/>
                <counts group_id="E3" events="6" subjects_affected="6" subjects_at_risk="52"/>
                <counts group_id="E4" events="3" subjects_affected="3" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Blood Creatine Phosphokinase Increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" events="6" subjects_affected="4" subjects_at_risk="109"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Neutrophil Count Decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" events="5" subjects_affected="3" subjects_at_risk="109"/>
                <counts group_id="E3" events="4" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E4" events="4" subjects_affected="2" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Protein Urine Present</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" events="5" subjects_affected="4" subjects_at_risk="109"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="52"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Weight Decreased</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="57"/>
                <counts group_id="E2" events="7" subjects_affected="6" subjects_at_risk="109"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="52"/>
                <counts group_id="E4" events="5" subjects_affected="3" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Weight Increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" events="4" subjects_affected="3" subjects_at_risk="109"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E4" events="3" subjects_affected="2" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>White Blood Cell Count Decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" events="8" subjects_affected="5" subjects_at_risk="109"/>
                <counts group_id="E3" events="5" subjects_affected="2" subjects_at_risk="52"/>
                <counts group_id="E4" events="6" subjects_affected="5" subjects_at_risk="100"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased Appetite</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="109"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E4" events="3" subjects_affected="3" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Vitamin D Deficiency</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="57"/>
                <counts group_id="E2" events="4" subjects_affected="3" subjects_at_risk="109"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E4" events="4" subjects_affected="4" subjects_at_risk="100"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="7" subjects_affected="3" subjects_at_risk="57"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="109"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="52"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Back Pain</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="57"/>
                <counts group_id="E2" events="6" subjects_affected="5" subjects_at_risk="109"/>
                <counts group_id="E3" events="3" subjects_affected="2" subjects_at_risk="52"/>
                <counts group_id="E4" events="5" subjects_affected="3" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Muscle Spasms</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="57"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="109"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="52"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Muscular Weakness</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="57"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="109"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="52"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Pain In Extremity</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="57"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="109"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E4" events="3" subjects_affected="3" subjects_at_risk="100"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Disturbance In Attention</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="57"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="109"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="57"/>
                <counts group_id="E2" events="9" subjects_affected="9" subjects_at_risk="109"/>
                <counts group_id="E3" events="12" subjects_affected="6" subjects_at_risk="52"/>
                <counts group_id="E4" events="3" subjects_affected="2" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="18" subjects_affected="13" subjects_at_risk="57"/>
                <counts group_id="E2" events="30" subjects_affected="18" subjects_at_risk="109"/>
                <counts group_id="E3" events="22" subjects_affected="7" subjects_at_risk="52"/>
                <counts group_id="E4" events="28" subjects_affected="14" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Hypoaesthesia</sub_title>
                <counts group_id="E1" events="5" subjects_affected="3" subjects_at_risk="57"/>
                <counts group_id="E2" events="7" subjects_affected="6" subjects_at_risk="109"/>
                <counts group_id="E3" events="4" subjects_affected="3" subjects_at_risk="52"/>
                <counts group_id="E4" events="4" subjects_affected="3" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Paraesthesia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" events="19" subjects_affected="11" subjects_at_risk="109"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E4" events="7" subjects_affected="4" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Presyncope</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="109"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="109"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="52"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Tremor</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="57"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="109"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="52"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="100"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="57"/>
                <counts group_id="E2" events="6" subjects_affected="4" subjects_at_risk="109"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E4" events="3" subjects_affected="2" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="57"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="109"/>
                <counts group_id="E3" events="4" subjects_affected="4" subjects_at_risk="52"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="57"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="109"/>
                <counts group_id="E3" events="3" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="100"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Micturition Urgency</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="109"/>
                <counts group_id="E3" events="6" subjects_affected="5" subjects_at_risk="52"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Pollakiuria</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="109"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="52"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="100"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Dysmenorrhoea</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="57"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="109"/>
                <counts group_id="E3" events="4" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E4" events="5" subjects_affected="2" subjects_at_risk="100"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="57"/>
                <counts group_id="E2" events="6" subjects_affected="5" subjects_at_risk="109"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="52"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="109"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Nasal Congestion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="109"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Oropharyngeal Pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="57"/>
                <counts group_id="E2" events="8" subjects_affected="7" subjects_at_risk="109"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="52"/>
                <counts group_id="E4" events="9" subjects_affected="7" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Respiratory Disorder</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E3" events="3" subjects_affected="2" subjects_at_risk="52"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Rhinitis Allergic</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="109"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="100"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Acne</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="57"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="109"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E4" events="5" subjects_affected="4" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="57"/>
                <counts group_id="E2" events="26" subjects_affected="24" subjects_at_risk="109"/>
                <counts group_id="E3" events="10" subjects_affected="9" subjects_at_risk="52"/>
                <counts group_id="E4" events="10" subjects_affected="10" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Dry Skin</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="52"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Eczema</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="109"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E4" events="4" subjects_affected="3" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="57"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="109"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="52"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="100"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Orthostatic Hypotension</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="57"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="100"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The Sponsor supports publication of clinical trial results but may request that investigators temporarily delay or alter publications in order to protect proprietary information. The Sponsor may also require that the results of multicenter studies be published only in their entirety and not as individual site data.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Trial Transparency Team</name_or_title>
      <organization>Genzyme, a Sanofi Company</organization>
      <phone>800-633-1610 ext 6#</phone>
      <email>Contact-US@sanofi.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/NCT02201108
org study id: EFC11759
secondary id: 2011-005249-12
secondary id: U1111-1124-0983
nct id: NCT02201108
lead sponsor: 
has dmc: Yes
Primary Objective:

      To assess the effect of teriflunomide in comparison to placebo on disease activity measured
      by time to first clinical relapse after randomization in children and adolescents 10 to 17
      years of age with relapsing forms of multiple sclerosis (MS).

      Secondary Objective:

        -  To assess the effect of teriflunomide in comparison to placebo on disease
           activity/progression measured by brain magnetic resonance imaging (MRI) and on cognitive
           function.

        -  To evaluate the safety and tolerability of teriflunomide in comparison to placebo.

        -  To evaluate the pharmacokinetics (PK) of teriflunomide.
The study duration included a screening period up to 4 weeks, a double-blind treatment period
      of up to 96 weeks, an open-label period which included the remainder of the initial 96 weeks,
      where applicable, and a 96-week extension, i.e., up to a maximum of 192 weeks after
      randomization. There was a follow-up period of 4 weeks for participants discontinuing
      treatment.

      Within the 96 weeks double-blind treatment period, the first 4 weeks were PK run-in phase in
      which PK samples (blood samples) were collected from participants and then 4 weeks of
      analysis (no samples drawn). The PK run-in phase (total 8 weeks) was intended to provide
      individual PK parameters to allow the dose adjustment to the 14 milligrams (mg)
      adult-equivalent dose for the rest of the study.

      Participants who experienced a relapse after the PK run-in phase (8 weeks) and confirmed by
      the Relapse Adjudication Panel and participants who fulfilled MRI criteria (high number of
      new lesions at weeks 36, 48 or 72 compared to previous images) had the option to continue in
      an open-label teriflunomide treatment arm up to 192 weeks from randomization.

      An optional additional extension period is available for young participants with
      teriflunomide until the participants are 18 years old and/or able to switch to commercial
      product, whichever comes first.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Time to First Confirmed Clinical Relapse
time frame: Baseline up to Week 96
description: Time to first clinical relapse was defined as the duration (in weeks) between randomization and first confirmed clinical relapse. Clinical relapses were defined as new or recurrent neurological symptoms not associated with fever or infection, lasting at least 24 hours, and accompanied by new objective neurological findings upon neurological examination and documented by a standardized, quantified functional system score (FSSs) which included 8 items and items were rated on different scales: brain stem, cerebellar and cerebral functions rated on a scale of 0 to 5; visual, pyramidal, sensory and bowel/bladder rated on a scale of 0 to 6 and ambulation on a scale of 0 to 12, where higher score in each scale indicated worsened neurological function. Confirmed clinical relapse were reviewed and confirmed by an independent Relapse Adjudication Panel (RAP). A participant without confirmed clinical relapse, was considered as clinical relapse free until the end of Week 96.
measure: Probability of Participants Who Were Clinical Relapse Free at Weeks 24, 48, 72, 96, 120, 144, 168 and 192
time frame: Weeks 24, 48, 72, 96, 120, 144, 168 and 192
description: Participant was considered free of clinical relapse if the participant had no confirmed clinical relapse before treatment discontinuation/completion in 192 weeks treatment period. Clinical relapses: new/recurrent neurological symptoms not associated with fever/infection, lasted at least 24 hours, and accompanied by new objective neurological findings upon neurological examination and documented by standardized, quantified FSSs which included 8 items: rated on different scales: brain stem, cerebellar and cerebral functions rated on scale of 0 to 5; visual, pyramidal, sensory and bowel/bladder rated on scale of 0 to 6 & ambulation on scale of 0 to 12, where higher score in each scale indicated worsened neurological function. New/recurrent symptoms occurred less than 30 days following onset of relapse were considered part of same relapse. Probability of participants who were clinical relapse free at specified weeks were estimated by Kaplan-Meier method and reported.
measure: Brain Magnetic Resonance Imaging (MRI) Assessment: Number of New or Enlarged T2 Lesions Per MRI Scan
time frame: Baseline up to Week 192
description: Number of new or enlarged T2 lesions per scan was defined as the total number of new or enlarged T2 lesion that occurred during the 192 weeks treatment period divided by the total number of scans performed during 192 weeks. To account for the different numbers of scans performed among the participants, a negative binomial regression model with robust variance estimation was used. The model included the total number of new or enlarged T2-lesions as the response variable, with treatment group, region, pubertal status and age as covariates and log-transformed number of scans as an offset variable.
measure: Brain Magnetic Resonance Imaging Assessment: Number of T1 Gadolinium (Gd)-Enhancing T1 Lesions Per MRI Scan
time frame: Baseline up to Week 192
description: The number of T1 Gd-Enhancing lesions per scan was defined as the total number of Gd-enhancing lesions that occurred during the 192 weeks treatment period divided by the total number of scans performed during 192 weeks. To account for the different number of scans performed among the participants, a negative binomial regression model with robust variance estimation was used. The model included the total number of T1-lesions as the response variable, with treatment group, region, pubertal status and age as covariates and log-transformed number of scans as an offset variable.
measure: Brain Magnetic Resonance Imaging Assessment: Change From Baseline in Volume of T2 Lesions at Weeks 24, 36, 48, 72, 96, 144 and 192
time frame: Baseline, DB period: Weeks 24, 36, 48, 72 and 96; OL period: Weeks 48, 96, 144 and 192
description: Volume of T2 lesions was measured by MRI scan.
measure: Brain Magnetic Resonance Imaging Assessment: Change From Baseline in Volume of T1 Hypointense Lesions
time frame: Baseline, DB period: Weeks 24, 36, 48, 72 and 96; OL period: Weeks 48, 96, 144 and 192
description: Volume of T1 hypointense lesions was measured by MRI scan.
measure: Brain Magnetic Resonance Imaging Assessment: Number of New T1 Hypointense Lesions Per MRI Scan
time frame: Baseline up to Week 192
description: The number of new T1 hypointense lesions were obtained from MRI scans.
measure: Brain Magnetic Resonance Imaging Assessment: Percentage of Participants Free of New or Enlarged MRI T2-Lesions
time frame: Baseline, Weeks 24, 48, 72, 96, 144 and 192
description: Percentage of participants who were free of new or enlarged T2 lesions at Weeks 24, 48, 72, 96, 144 and 192 were reported.
measure: Brain Magnetic Resonance Imaging Assessment: Percent Change From Baseline in Brain Volume at Weeks 24, 36, 48, 72, 96, 144 and 192
time frame: Baseline, DB period: Weeks 24, 36, 48, 72 and 96; OL period: Weeks 48, 96, 144 and 192
description: Percent change from baseline in brain volume (assessed using MRI scans of the Brain) at Weeks 24, 36, 48,72, 96, 144 and 192 was reported.
measure: Cognitive Assessment: Change From Baseline in Total Number of Correct Substitutions Measured by Symbol Digit Modalities Test (SDMT) at Weeks 24, 48, 72, 96, 120, 144, 168 and 192
time frame: Baseline, DB period: Weeks 24, 48, 72 and 96; OL period: Weeks 24, 48, 72, 96, 120, 144, 168 and 192
description: SDMT measures the time to pair abstract symbols with specific numbers. It is a simple substitution task that gives the examinee 90 seconds to pair specific numbers with given geometric figures as a measure for screening cognitive impairment. The SDMT score is the number of correct substitution and ranged from 0 (worst outcome) to 110 (best outcome), where higher score indicated better cognitive function.
measure: Cognitive Assessment: Change From Baseline in Number of Completed Items Measured by Symbol Digit Modalities Test at Weeks 24, 48, 72, 96, 120, 144, 168 and 192
time frame: Baseline, DB period: Weeks 24, 48, 72 and 96; OL period: Weeks 24, 48, 72, 96, 120, 144, 168 and 192
description: SDMT measures the time to pair abstract symbols with specific numbers. It is a simple substitution task that gives the examinee 90 seconds to pair specific numbers with given geometric figures as a measure for screening cognitive impairment. The SDMT score is the number of completed items and ranged from 0 (worst outcome) to 110 (best outcome), where higher score indicated better cognitive function.
measure: Cognitive Assessment: Change From Baseline in Brief Visuospatial Memory Test-Revised (BVMT-R) Scores at Weeks 96 and 192
time frame: Baseline, Weeks 96 and 192
description: The BVMT consists of three trials in which participants must recall shapes by drawing figures on a blank page (response booklet) after being given the opportunity to memorize the figures (given in BMVT-R form) for 10 seconds. BMVT-R form consists of six figures. Points are awarded based on the accuracy of the drawn figure and by correct placement on the blank page. A minimum of 0 to 12 points/scores are awarded per trial, so a participant can score between 0 and 36 points for all three trials (by adding the points/score from each trial), where higher score indicates better outcome.
measure: Cognitive Assessment: Change From Baseline in Trail Making Test- Part A (TMT-A) Test Scores (in Seconds) at Week 96 and 192
time frame: Baseline, Weeks 96 and 192
description: 'Trail Making Test Part A' is a neuropsychological test of visual attention and task switching. The task requires a participant to 'connect-the-dots' of 25 consecutive numbers (1,2, 3, etc.) in sequential order on a sheet of paper or computer screen. The goal of the participant is to finish the test as quickly as possible, and the time taken to complete the test used as the primary performance metric (in seconds). This is a timed test and the number of seconds to complete the task is recorded. Maximum time allowed is 300 seconds. A lower score indicated better cognitive function.
measure: Cognitive Assessment: Change From Baseline in Trail Making Test B (TMT-B) Test Scores (in Seconds) at Weeks 96 and 192
time frame: Baseline, Weeks 96 and 192
description: TMT-B is a cognitive test that gives a measure of various aspects of cognitive performance. It is used to measure cognitive fatigue. The test consisted of 25 circles containing 13 sequential numbers (1 to 13) and 12 sequential letters (A to L) positioned. The test evaluates the time (in seconds) to correctly order letters and numbers in alternate order (1, A, 2, B etc.). Maximum time allowed is 300 seconds, where less time/lower score indicated better cognitive function/performance.
measure: Cognitive Assessment: Change From Baseline in Beery Visual-motor Integration (BVMI) Scores at Weeks 96 and 192
time frame: Baseline, Weeks 96 and 192
description: The Beery VMI is a non-verbal assessment that assessed the extent to which individuals can integrate their visual and motor abilities. The participants were provided with geometric designs ranging from simple line drawings to more complex figures and were asked to copy the designs. The test consisted of 24 figures. One point was scored for each successful copy of drawings and no scoring was given when the participant failed to copy the drawings properly. Each successful copying of drawings was summed up and the total was scored on a scale ranged from 0 to 24, where higher score indicated better visual construction skills/better visual and motor abilities and lower score indicated poor visual construction skills/poor visual and motor abilities.
measure: Cognitive Assessment: Change From Baseline in Wechsler Abbreviated Scale of Intelligence-II (WASI-II) Vocabulary Total Raw Scores at Weeks 96 and 192
time frame: Baseline, Weeks 96 and 192
description: The WASI-II: Vocabulary test is a quick estimate of an individual's level of intellectual functioning which comprised of 31 total items that required the participant to orally define 3 images and 28 words presented both orally and visually. Items 1 to 3 rated on a score of 0 or 1, items 4 and 5 rated on a score of 0 or 2, items 6 to 31 rated on a scale of 0 to 2. Each item score was summed up to derive the total score which ranged from 0 (minimum score) to 59 (maximum score), where higher score indicated better level of intellectual functioning/higher level of intelligence.
measure: Cognitive Assessment: Change From Baseline in Delis-Kaplan Executive Function System (D-KEFS) Letter Fluency Total Correct Raw Score at Weeks 96 and 192
time frame: Baseline, Weeks 96 and 192
description: Letter Fluency is a condition measured in the D-KEFS. Participants were asked to name as many words as they can, starting with a specified letter for 60 seconds. The words cannot be names, places, numbers or grammatical variants of previous answers. Repeated answers were not scored as a correct response. There were 3 trials, with 3 different letters. The total number of correct responses was totaled for all 3 trials and a letter fluency score was given. A higher score was considered better. There was no set range as the score depends on how many correct words the participant relays in the given time period.
measure: Cognitive Assessment: Change From Baseline in Delis-Kaplan Executive Function System Category Fluency Total Correct Raw Score at Weeks 96 and 192
time frame: Baseline, Weeks 96 and 192
description: Category Fluency is a condition measured in the D-KEFS. It measured participant's ability to generate words from three different categories (e.g., fruits, vegetables and animals), within a minute for each category. Total score was number of correct words for each category with no points for repetitions or non-words. Score ranged from 0 to unlimited, where 0 = low score, higher score indicated better performance.
measure: Cognitive Assessment - Selective Reminding Test (SRT): Change From Baseline in Total Number of Words on Delayed Recall at Weeks 96 and 192
time frame: Baseline, Weeks 96 and 192
description: SRT is a test to assess verbal learning and memory. During the administration of the SRT only the examiner and the participant should be in the testing room. A list of twelve words was read aloud by the examiner at a rate of one word per two seconds. The participant is asked to recall all twelve words after a 30 minute delay. Only the words that were missed on the preceding trial were given in the consecutive trial. The total score represented a sum score of total 6 trials, therefore the score range was from 0 to 72. The lower the score the worse the outcome, higher score indicated better recall.
measure: DB: Pharmacokinetics: Steady-state Trough Concentration (Ctrough) of Teriflunomide
time frame: Predose on Week 36
description: Ctrough was defined as the concentration reached by the drug before the next dose administered. Data for this outcome measure was planned to be collected and analyzed separately for each dose of Teriflunomide. PK samples for teriflunomide 3.5 mg were collected during the first 8 weeks but all participants were switched to teriflunomide 7 mg after Week 8. Hence, plasma concentration of teriflunomide 7 mg and 14 mg were reported.
measure: OL: Time to First Confirmed Clinical Relapse
time frame: Baseline up to Week 192
description: Time to first clinical relapse was defined as duration (in weeks) after enrollment in OL period and first confirmed clinical relapse. Clinical relapses were defined as new or recurrent neurological symptoms not associated with fever or infection, lasted at least 24 hours and accompanied by new objective neurological findings upon neurological examination and documented by standardized, quantified FSSs which included 8 items and items were rated on different scales: brain stem, cerebellar & cerebral functions rated on scale of 0 to 5; visual, pyramidal, sensory and bowel/bladder rated on scale of 0 to 6 and ambulation on scale of 0 to 12 where higher score in each scale indicated worsened neurological function. Confirmed clinical relapse were reviewed and confirmed by independent RAP. Participant without confirmed clinical relapse, was considered as clinical relapse free until end of Week 192.
measure: OL: Pharmacokinetics: Steady-state Trough Concentration (Ctrough) of Teriflunomide
time frame: Pre-dose at Week 36
description: Ctrough was defined as the concentration reached by the drug before the next dose is administered. Data for this outcome measure was planned to be collected and analyzed separately for each dose of teriflunomide. PK samples for teriflunomide 3.5 mg were collected during the first 8 weeks but all participants were switched to teriflunomide 7 mg after Week 8. Hence, plasma concentration of teriflunomide 7 mg and 14 mg were reported.
arm group label: Placebo
arm group type: Placebo Comparator
description: Matching placebo tablets
arm group label: Teriflunomide
arm group type: Experimental
description: Teriflunomide oral tablet, three dosages (3.5, 7 or 14 mg) to reach 14 mg adult equivalent
intervention type: Drug
intervention name: Teriflunomide
description: Pharmaceutical form:film-coated tablet, Route of administration: oral
arm group label: Teriflunomide
other name: AUBAGIO, HMR1726
intervention type: Drug
intervention name: Placebo
description: Pharmaceutical form:tablet, Route of administration: oral
arm group label: Placebo
criteria: 
gender: All
minimum age: 10 Years
maximum age: 17 Years
healthy volunteers: No
last name: Clinical Sciences & Operations
role: Study Director
affiliation: Sanofi
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country: Belgium
country: Bulgaria
country: Canada
country: China
country: Estonia
country: France
country: Greece
country: Israel
country: Lebanon
country: Lithuania
country: Morocco
country: Netherlands
country: Portugal
country: Russian Federation
country: Serbia
country: Spain
country: Tunisia
country: Turkey
country: Ukraine
country: United Kingdom
country: United States
country: Australia
country: Macedonia, The Former Yugoslav Republic of
country: North Macedonia
country: Poland
country: Slovenia
responsible party type: Sponsor
mesh term: Multiple Sclerosis
mesh term: Sclerosis
mesh term: Teriflunomide
sharing ipd: Yes
ipd description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
provided document: 
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participant flow: 
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outcome list: 
reported events: 
certain agreements: 
point of contact: 