<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/NCT01700387</url>
  </required_header>
  <id_info>
    <org_study_id>12-001AL</org_study_id>
    <secondary_id>71403</secondary_id>
    <nct_id>NCT01700387</nct_id>
  </id_info>
  <brief_title>A Study to Evaluate the Tolerability of Botox and Topiramate or Botox and Placebo and Effect on Cognitive Efficiency</brief_title>
  <official_title>A Randomized, Pilot Study to Evaluate the Tolerability of OnabotulinumtoxinA Plus Topiramate vs. OnabotulinumtoxinA Plus Placebo and Long Term Effect of Treatment on Cognitive Efficiency and Continuation of Care</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cady, Roger, M.D.</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Allergan</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Cady, Roger, M.D.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate sustained tolerability, quality of life, and change&#xD;
      in cognitive efficiency following treatment with OnabotulinumtoxinA and daily topiramate vs.&#xD;
      OnabotulinumtoxinA and daily placebo (Group A vs. Group B).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Numerous migraine preventive medications are well known to be associated with cognitive&#xD;
      impairment and disruption of mood.&#xD;
&#xD;
      Clinvest would propose a pilot study of chronic migraine patients randomized 1:1 to&#xD;
      onabotulinumtoxinA and daily topiramate or onabotulinumtoxinA and placebo. This pilot study&#xD;
      will examine the degree to which subjects are able to tolerate and are satisfied with a&#xD;
      migraine preventive medication in addition to onabotulinumtoxinA over an extended period of&#xD;
      time and the effect of the subjects' quality of life compared with onabotulinumtoxinA as a&#xD;
      single therapy. It will also assess short and long term effects of these two treatments on&#xD;
      cognition. Cognitive performance will be measured by the Mental Efficiency Workload Test&#xD;
      (MEWT), a repeated measures handheld neuropsychological test battery that measures mental&#xD;
      efficiency via 4 sub-tests (Simple Reaction Time, Running Memory, Continuous Performance&#xD;
      Task, Matching to Sample, and Mathematical Processing) to demonstrate short and long term&#xD;
      changes in mental status compared to their baseline. The Controlled Oral Word Association&#xD;
      Test (COWAT) will be used to test verbal fluency and screen for anomic aphasia, a known side&#xD;
      effect of several migraine prophylactic medications including topiramate.&#xD;
&#xD;
      Visit 1 - Screening / Baseline Following Informed Consent a medical, headache, and medication&#xD;
      history will be collected and a physical and neurological exam performed on all subjects. A&#xD;
      urine pregnancy test will be collected from any subject of child-bearing potential. Vital&#xD;
      signs and ECG (at the discretion of the investigator) will be completed. The Mental&#xD;
      Efficiency Workload Test (MEWT) will be administered 3 times to establish a cognitive&#xD;
      efficiency baseline. The COWAT will be completed. Subjects will be instructed regarding&#xD;
      completion of the online 1-month Baseline Period Migraine Diary and be instructed to treat&#xD;
      headaches during the 1-month Baseline Period with their usual acute migraine medication in&#xD;
      their usual manner.&#xD;
&#xD;
      Visit 2 - Randomization / Injection Following the 1-month Baseline Period, any change in&#xD;
      medical or medication history since the previous visit will be collected and a pregnancy test&#xD;
      collected if appropriate. Vital signs will be recorded. Subjects continuing to meet&#xD;
      eligibility criteria will be instructed to complete the online Treatment Period Migraine&#xD;
      Diary daily. The MEWT, HIT-6, Migraine Specific Questionnaire (MSQ) and COWAT will be&#xD;
      completed. The coordinator will assess compliance with online headache diary and any&#xD;
      deviation outside of 100% compliance should be documented at the site. If in the&#xD;
      investigator's opinion, the subject maintained a high level of compliance with the online&#xD;
      headache diary, subjects will then be randomized into the study.&#xD;
&#xD;
      Eligible subjects will be randomized 1:1 in a blinded fashion to receive onabotulinumtoxinA&#xD;
      at 31 fixed-site, fixed-dose injections across seven (7) specific head/neck muscle areas and&#xD;
      daily topiramate (Group A) or onabotulinumtoxinA at 31 fixed-site, fixed-dose injections&#xD;
      across seven (7) specific head/neck muscle areas and placebo to match topiramate (Group B).&#xD;
&#xD;
      Daily study medication (topiramate or placebo) will be dispensed for the following 3 months.&#xD;
&#xD;
      The Group A topiramate titration schedule will be as follows:&#xD;
&#xD;
      Week 1: topiramate 25 mg qhs (every night at bedtime) Week 2: topiramate 25 mg bid (twice a&#xD;
      day) Week 3: topiramate 25 mg q am (everyday before noon) + topiramate 50 mg qhs Week 4:&#xD;
      topiramate 50mg bid&#xD;
&#xD;
      Only one dosage adjustment (increase or decrease), based on efficacy or tolerability, may be&#xD;
      made at the investigator's discretion. Subjects must maintain a dose of at least 50 mg/day to&#xD;
      remain in the Treatment Period.&#xD;
&#xD;
      The Group B placebo schedule will be as following:&#xD;
&#xD;
      Week 1: 1 tab qhs Week 2: 1 tab bid Week 3: 1 tab q am + 2 tabs qhs Week 4: 2 tabs bid&#xD;
&#xD;
      Subjects will be instructed to complete the online daily Treatment Period Migraine Diary&#xD;
      during the next 3-month period.&#xD;
&#xD;
      Following Visit 2, subjects will be phoned monthly and any adverse events collected. Subjects&#xD;
      will also be sent weekly reminders for 8 weeks following Visit 2 via email to take study&#xD;
      medication, complete online diary and contact their coordinator for any questions or concerns&#xD;
      they may have. During the titration period, any subject in Group A experiencing an adverse&#xD;
      event thought to be related to study medication dosage will return to the clinic at an&#xD;
      Unscheduled Visit for dosage adjustment.&#xD;
&#xD;
      Visit 3&#xD;
&#xD;
      Three months following Visit 2, subjects will return and complete the MEWT, HIT-6, MSQ,&#xD;
      COWAT, and Subject's Global Impression of Change (SGIC). The Investigator will complete a&#xD;
      Physician's Global Impression of Change (PGIC). Any change in medical or medication history&#xD;
      since the previous visit will be collected and a pregnancy test collected if appropriate.&#xD;
      Vital signs will be recorded. The coordinator will assess compliance with online headache&#xD;
      diary and any deviation outside of 100% compliance should be documented at the site. If in&#xD;
      the investigator's opinion, the subject maintained a high level of compliance with the online&#xD;
      headache diary, subjects will be allowed to continue in the study.&#xD;
&#xD;
      All subjects will be administered a dose of 155 U onabotulinumtoxinA at 31 fixed-site,&#xD;
      fixed-dose injections across seven (7) specific head/neck muscle areas.&#xD;
&#xD;
      Any unused study medication and used packaging will be collected, drug accountability will be&#xD;
      performed, and daily study medication (topiramate or placebo) will be dispensed for the&#xD;
      following 3 months.&#xD;
&#xD;
      Subjects will be instructed to complete the online daily Treatment Period Migraine Diary&#xD;
      during the next 3-month period.&#xD;
&#xD;
      Following Visit 3, subjects will be phoned monthly and any adverse events collected.&#xD;
&#xD;
      Visit 4&#xD;
&#xD;
      Three months following Visit 3, subjects will return and complete the MEWT, HIT-6, MSQ,&#xD;
      COWAT, and Subject's Global Impression of Change (SGIC). The Investigator will complete a&#xD;
      Physician's Global Impression of Change (PGIC). Any change in medical or medication history&#xD;
      since the previous visit will be collected and a pregnancy test collected if appropriate.&#xD;
      Vital signs will be recorded. The coordinator will assess compliance with online headache&#xD;
      diary and any deviation outside of 100% compliance should be documented at the site.&#xD;
&#xD;
      All subjects will be administered a dose of 155 U onabotulinumtoxinA at 31 fixed-site,&#xD;
      fixed-dose injections across seven (7) specific head/neck muscle areas.&#xD;
&#xD;
      Any unused study medication and used packaging will be collected, drug accountability will be&#xD;
      performed, and daily study medication (topiramate or placebo) will be dispensed for the&#xD;
      following 3 months.&#xD;
&#xD;
      Subjects will be instructed to complete the online daily Treatment Period Migraine Diary&#xD;
      during the next 3-month period.&#xD;
&#xD;
      Following Visit 4, subjects will be phoned monthly and any adverse events collected.&#xD;
&#xD;
      Visit 5&#xD;
&#xD;
      Three months following Visit 4, subjects will return and complete the MEWT, HIT-6, MSQ,&#xD;
      COWAT, and Subject's Global Impression of Change (SGIC). The Investigator will complete a&#xD;
      Physician's Global Impression of Change (PGIC). Any change in medical or medication history&#xD;
      since the previous visit will be collected and a pregnancy test collected if appropriate.&#xD;
      Vital signs will be recorded. The coordinator will assess compliance with online headache&#xD;
      diary and any deviation outside of 100% compliance should be documented at the site.&#xD;
&#xD;
      All subjects will be administered a dose of 155 U onabotulinumtoxinA at 31 fixed-site,&#xD;
      fixed-dose injections across seven (7) specific head/neck muscle areas.&#xD;
&#xD;
      Any unused study medication and used packaging will be collected, drug accountability will be&#xD;
      performed, and daily study medication (topiramate or placebo) will be dispensed for the&#xD;
      following 3 months.&#xD;
&#xD;
      Subjects will be instructed to complete the online daily Treatment Period Migraine Diary&#xD;
      during the next 3-month period.&#xD;
&#xD;
      Following Visit 5, subjects will be phoned monthly and any adverse events collected.&#xD;
&#xD;
      Visit 6&#xD;
&#xD;
      Three months following Visit 5, subjects will return and complete the MEWT, HIT-6, MSQ,&#xD;
      COWAT, and Subject's Global Impression of Change. The Investigator will complete a&#xD;
      Physician's Global Impression of Change. Any change in medical or medication history since&#xD;
      the previous visit will be collected and a pregnancy test collected if appropriate. Vital&#xD;
      signs will be recorded. The coordinator will assess compliance with online headache diary and&#xD;
      any deviation outside of 100% compliance should be documented at the site.&#xD;
&#xD;
      Any unused study medication and used packaging will be collected and drug accountability will&#xD;
      be performed.&#xD;
&#xD;
      Subjects will exit the study at Visit 6.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2012</start_date>
  <completion_date type="Actual">August 2014</completion_date>
  <primary_completion_date type="Actual">August 2014</primary_completion_date>
  <phase>Phase 4</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>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Subject Attrition Post Randomization</measure>
    <time_frame>Collected on Visit 2 (Day 29) through Visit 6 (Day 365)</time_frame>
    <description>Count of subject attrition following randomization and reason for attrition (Consent withdrawn, Withdrawn due to adverse event, Lost to follow up)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Subject Global Impression of Change (SGIC)</measure>
    <time_frame>Collected on Visit 3 (Day 113), Visit 4 (Day 197), Visit 5 (281), and Visit 6 (Day 365)</time_frame>
    <description>Score on Subject Global Impression of Change at Visits 3-6 (Day 113 and 365). Likert scale ranging from 1-7, where 1 = extremely worse and 7 = extremely better.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Physician Global Impression of Change (PGIC)</measure>
    <time_frame>Collected on Visit 3 (Day 113), Visit 4 (Day 197), Visit 5 (281), and Visit 6 (Day 365)</time_frame>
    <description>Score on Physician Global Impression of Change at Visits 3-6 (Day 113 and 365). Likert scale ranging from 1-7, where 1 = extremely worse and 7 = extremely better.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Subject's Controlled Oral Word Association Test (COWAT) Score Percent Change Compared From Baseline to Visits 3-6</measure>
    <time_frame>Baseline, Visit 3 (Day 113) through Visit 6 (Day 365)</time_frame>
    <description>The Controlled Oral Word Association Test (COWAT) is a measure of verbal fluency. Raw COWAT scores have a lower bound of 0 with no upper bound. Higher scores indicate better verbal fluency. COWAT score percent change from baseline will be reported. Positive change scores represent better verbal fluency compared to baseline.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Headache Days</measure>
    <time_frame>Baseline and Months 1-12</time_frame>
    <description>Number of Headache Days reported in 30-day Baseline Period and Treatment Period Months 1-12</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Headache Impact Test (HIT-6) Scores at Visits 2-6 to Measure Effect of Headache in Subject's Life</measure>
    <time_frame>Collected on Visit 2 (Day 29), 3 (Day 113), Visit 4 (Day 197), Visit 5 (281), and Visit 6 (Day 365)</time_frame>
    <description>The Headache Impact Test (HIT-6) is a tool used to measure the impact headaches have on an individual's ability to function on the job, at school, at home and in social situations. The HIT-6 score range is from 36 to 78 with higher scores indicating greater impact (worse outcome).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MEWT Simple Reaction Time Sub-test Score Percent Change Compared From Baseline to Visits 3-6</measure>
    <time_frame>Baseline, Visit 3 (Day 113), Visit 4 (Day 197), Visit 5 (281), and Visit 6 (Day 365)</time_frame>
    <description>The Mental Efficiency Workload Test (MEWT) is a cognitive functioning scale with four sub-scales (Simple Reaction Time, Running Memory Continuous Performance Task, Matching to Sample, and Mathematical Processing). Each sub-scale has a minimum and maximum values of 1 to 10, 1 indicates the poorest level and 10 indicates the best level of cognitive functioning. MEWT sub-scale score percent change from baseline will be reported. Positive change scores represent better cognitive functioning compared to baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MEWT Running Memory Continuous Performance Task Sub-test Score Percent Change Compared From Baseline to Visits 3-6</measure>
    <time_frame>Baseline, Visit 3 (Day 113), Visit 4 (Day 197), Visit 5 (281), and Visit 6 (Day 365)</time_frame>
    <description>The Mental Efficiency Workload Test (MEWT) is a cognitive functioning scale with four sub-scales (Simple Reaction Time, Running Memory Continuous Performance Task, Matching to Sample, and Mathematical Processing). Each sub-scale has a minimum and maximum values of 1 to 10, 1 indicates the poorest level and 10 indicates the best level of cognitive functioning. MEWT sub-scale score percent change from baseline will be reported. Positive change scores represent better cognitive functioning compared to baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MEWT Matching to Sample Sub-test Score Percent Change Compared From Baseline to Visits 3-6</measure>
    <time_frame>Baseline, Visit 3 (Day 113), Visit 4 (Day 197), Visit 5 (281), and Visit 6 (Day 365)</time_frame>
    <description>The Mental Efficiency Workload Test (MEWT) is a cognitive functioning scale with four sub-scales (Simple Reaction Time, Running Memory Continuous Performance Task, Matching to Sample, and Mathematical Processing). Each sub-scale has a minimum and maximum values of 1 to 10, 1 indicates the poorest level and 10 indicates the best level of cognitive functioning. MEWT sub-scale score percent change from baseline will be reported. Positive change scores represent better cognitive functioning compared to baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MEWT Mathematical Processing Sub-test Score Percent Change Compared From Baseline to Visits 3-6</measure>
    <time_frame>Baseline, Visit 3 (Day 113), Visit 4 (Day 197), Visit 5 (281), and Visit 6 (Day 365)</time_frame>
    <description>The Mental Efficiency Workload Test (MEWT) is a cognitive functioning scale with four sub-scales (Simple Reaction Time, Running Memory Continuous Performance Task, Matching to Sample, and Mathematical Processing). Each sub-scale has a minimum and maximum values of 1 to 10, 1 indicates the poorest level and 10 indicates the best level of cognitive functioning. MEWT sub-scale score percent change from baseline will be reported. Positive change scores represent better cognitive functioning compared to baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Subject Estimation of Compliance With Daily Study Drug</measure>
    <time_frame>Collected on Visit 2 (Day 29), 3 (Day 113), Visit 4 (Day 197), and Visit 5 (281)</time_frame>
    <description>Subject estimation of compliance with daily study drug during the study period. Compliance ranges from 0% to 100% with higher percentages indicating greater compliance with study drug.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Non-Serious Adverse Events Between Groups</measure>
    <time_frame>13 Months (Visit 1 to Visit 6)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Subject's Migraine Specific Quality of Life Questionnaire (MSQ) Scores at Baseline, 3, 6, 9 and 12 Months to Measure Subject's Quality of Life</measure>
    <time_frame>Baseline, Months: 3, 6, 9 and 12</time_frame>
    <description>The Migraine-Specific Quality of Life Questionnaire (MSQ) is a scale that measures the impact of migraine across three aspects: role function-restrictive (RR), role function-preventive (RP), and emotional function (EF). Possible scores on each sub-scale range from a 0 to 100 scale such that higher scores indicate better quality of life.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Chronic Migraine</condition>
  <arm_group>
    <arm_group_label>OnabotulinumtoxinA + Topiramate</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subject will receive 155 U onabotulinumtoxinA injections at 31 sites every 3 months for 12 months and treat daily with topiramate. During the first month of the treatment period, subjects will titrate as follows:&#xD;
Week 1: topiramate 25 mg qhs Week 2: topiramate 25 mg bid Week 3: topiramate 25 mg q am + topiramate 50 mg qhs Week 4: topiramate 50 mg bid Only one dosage adjustment (increase or decrease), based on efficacy or tolerability, may be made at the investigator's discretion. Subjects must maintain a dose of at least 50 mg/day to remain in the Treatment Period.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>OnabotulinumtoxinA + Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Subject will receive 155 U onabotulinumtoxinA injections at 31 sites every 3 months for 12 months and treat daily with placebo. During the first month of the treatment period, subjects will titrate as follows:&#xD;
Week 1: 1 tab qhs Week 2: 1 tab bid Week 3: 1 tab q am + 2 tabs qhs Week 4: 2 tabs bid</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>onabotulinumtoxinA</intervention_name>
    <description>All subjects will receive a minimum dose of 155 U Botulinum Toxin Type A Purified Neurotoxin Complex administered at 31 fixed-site, fixed-dose injections across seven (7) specific head/neck muscle areas at Visits 2-5.</description>
    <arm_group_label>OnabotulinumtoxinA + Placebo</arm_group_label>
    <arm_group_label>OnabotulinumtoxinA + Topiramate</arm_group_label>
    <other_name>Botox, Botulinum Toxin Type A Purified Neurotoxin Complex</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Topiramate</intervention_name>
    <description>Subjects randomized to the onabotulinumtoxinA + topiramate group will receive:&#xD;
Week 1: topiramate 25 mg qhs Week 2: topiramate 25 mg bid Week 3: topiramate 25 mg q am + topiramate 50 mg qhs Week 4: topiramate 50 mg bid Only one dosage adjustment (increase or decrease), based on efficacy or tolerability, may be made at the investigator's discretion. Subjects must maintain a dose of at least 50 mg/day to remain in the Treatment Period.</description>
    <arm_group_label>OnabotulinumtoxinA + Topiramate</arm_group_label>
    <other_name>Topamax</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Subjects randomized to the onabotulinumtoxinA + placebo group will receive:&#xD;
Week 1: placebo 25 mg qhs Week 2: placebo 25 mg bid Week 3: placebo 25 mg q am + placebo 50 mg qhs Week 4: placebo 50 mg bid Only one dosage adjustment (increase or decrease), based on efficacy or tolerability, may be made at the investigator's discretion. Subjects must maintain a dose of at least 50 mg/day to remain in the Treatment Period.</description>
    <arm_group_label>OnabotulinumtoxinA + Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. must be outpatient, male or female, of any race, between 18 and 65 years of age.&#xD;
&#xD;
          2. if female of child bearing potential must have a negative pregnancy test result at the&#xD;
             Screening Visit and practice a reliable method of contraception.&#xD;
&#xD;
             A female is considered of childbearing potential unless she is post-menopausal for at&#xD;
             least 12 months prior to administration of study drug, without a uterus and/or both&#xD;
             ovaries or has been surgically sterilized for at least 6 months prior to study drug&#xD;
             administration.&#xD;
&#xD;
             Reliable methods of contraception are:&#xD;
&#xD;
             Complete abstinence from intercourse from 2 weeks prior to administration of the&#xD;
             investigational product. Throughout the study, and for a time interval (5 days) after&#xD;
             completion or premature discontinuation from the study. History of bilateral tubal&#xD;
             ligation Sterilization of male partner; or, Implants of levonorgestrel; or, Injectable&#xD;
             progestogen, or, Oral contraceptive (combination therapy with ethinyl estradiol plus a&#xD;
             progestin) with a placebo week every 1-3 months; or, Any intrauterine device (IUD)&#xD;
             with published data showing that the highest expected failure rate is less than 1% per&#xD;
             year (not all IUD's meet this criterion) in use at least 30 days prior to study drug&#xD;
             administration; or, Spermicide plus a mechanical barrier (e.g., spermicide plus a male&#xD;
             condom or a female diaphragm); or, Any other barrier methods (only is used in&#xD;
             combination with any of the above acceptable methods) in use at least 14 days prior to&#xD;
             study drug administration; or, Any other methods with published data showing that the&#xD;
             highest expected failure rate for that method is less than 1% per year.&#xD;
&#xD;
          3. must have history of chronic migraine (with or without aura) according to the criteria&#xD;
             proposed by the Headache Classification Committee of the International Headache&#xD;
             Society (IHS) for at least 3 months prior to enrollment.&#xD;
&#xD;
          4. must be able to understand the requirements of the study including maintaining a&#xD;
             headache Diary, and signing informed consent.&#xD;
&#xD;
          5. must be in good general health as determined by investigator.&#xD;
&#xD;
          6. if taking migraine preventive, must be on a stable dose of preventive medication for&#xD;
             at least 6 weeks prior to screening.&#xD;
&#xD;
          7. must have daily access to internet for completion of online daily headache diary.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. if female, is pregnant, planning to become pregnant during the study period, are&#xD;
             breast feeding, or are of childbearing potential and not practicing a reliable form of&#xD;
             birth control.&#xD;
&#xD;
          2. has headache disorders outside IHS-defined chronic migraine definition.&#xD;
&#xD;
          3. has evidence of underlying pathology contributing to their headaches.&#xD;
&#xD;
          4. has any medical condition that may increase their risk with exposure to&#xD;
             OnabotulinumtoxinA including diagnosed myasthenia gravis, Eaton-Lambert syndrome,&#xD;
             amyotrophic lateral sclerosis, or any other significant disease that might interfere&#xD;
             with neuromuscular function.&#xD;
&#xD;
          5. has profound atrophy or weakness of muscles in the target areas of injection.&#xD;
&#xD;
          6. has skin conditions or infections at any injection site.&#xD;
&#xD;
          7. has allergy or sensitivities to any component of the test medication.&#xD;
&#xD;
          8. has previously received onabotulinumtoxinA for migraine prevention.&#xD;
&#xD;
          9. has previously received topiramate.&#xD;
&#xD;
         10. who in the opinion of the investigator, has active major psychiatric or depressive&#xD;
             disorders including alcohol/drug abuse.&#xD;
&#xD;
         11. meets International Headache Society criteria for Medication Overuse Headache with&#xD;
             opioid or butalbital containing products.&#xD;
&#xD;
         12. who in the opinion of the investigator, is taking opioid or butalbital containing&#xD;
             products more than once a week that could be contributing to a pattern of increased&#xD;
             headaches or cognitive decline.&#xD;
&#xD;
         13. is planning or requiring surgery during the study.&#xD;
&#xD;
         14. has a history of poor compliance with medical treatment.&#xD;
&#xD;
         15. is currently participating in an investigational drug study or has participated in an&#xD;
             investigational drug study within the previous 30 days of the screening visit.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Roger K Cady, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Clinvest</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Clinvest/A Division of Banyan Group, Inc.</name>
      <address>
        <city>Springfield</city>
        <state>Missouri</state>
        <zip>65807</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <results_reference>
    <citation>Bootsma HP, Aldenkamp AP, Diepman L, Hulsman J, Lambrechts D, Leenen L, Majoie M, Schellekens A, de Krom M. The Effect of Antiepileptic Drugs on Cognition: Patient Perceived Cognitive Problems of Topiramate versus Levetiracetam in Clinical Practice. Epilepsia. 2006;47 Suppl 2:24-7. doi: 10.1111/j.1528-1167.2006.00683.x.</citation>
    <PMID>17105455</PMID>
  </results_reference>
  <results_reference>
    <citation>Kim SY, Lee HW, Jung DK, Suh CK, Park SP. Cognitive Effects of Low-dose Topiramate Compared with Oxcarbazepine in Epilepsy Patients. J Clin Neurol. 2006 Jun;2(2):126-33. doi: 10.3988/jcn.2006.2.2.126. Epub 2006 Jun 20.</citation>
    <PMID>20396496</PMID>
  </results_reference>
  <results_reference>
    <citation>Meador KJ, Loring DW, Vahle VJ, Ray PG, Werz MA, Fessler AJ, Ogrocki P, Schoenberg MR, Miller JM, Kustra RP. Cognitive and behavioral effects of lamotrigine and topiramate in healthy volunteers. Neurology. 2005 Jun 28;64(12):2108-14. doi: 10.1212/01.WNL.0000165994.46777.BE.</citation>
    <PMID>15985582</PMID>
  </results_reference>
  <verification_date>August 2020</verification_date>
  <study_first_submitted>October 1, 2012</study_first_submitted>
  <study_first_submitted_qc>October 2, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 4, 2012</study_first_posted>
  <results_first_submitted>October 7, 2014</results_first_submitted>
  <results_first_submitted_qc>October 7, 2014</results_first_submitted_qc>
  <results_first_posted type="Estimate">October 13, 2014</results_first_posted>
  <last_update_submitted>August 6, 2020</last_update_submitted>
  <last_update_submitted_qc>August 6, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">August 18, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Migraine</keyword>
  <keyword>Chronic Migraine</keyword>
  <keyword>Cognitive Efficiency</keyword>
  <keyword>Pilot Study</keyword>
  <keyword>Long Term Effect</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Migraine Disorders</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Topiramate</mesh_term>
    <mesh_term>Botulinum Toxins</mesh_term>
    <mesh_term>Botulinum Toxins, Type A</mesh_term>
    <mesh_term>abobotulinumtoxinA</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>OnabotulinumtoxinA + Topiramate</title>
          <description>Subject will receive 155 U onabotulinumtoxinA injections at 31 sites every 3 months for 12 months and treat daily with topiramate. During the first month of the treatment period, subjects will titrate as follows:&#xD;
Week 1: topiramate 25 mg qhs (every night at bedtime) Week 2: topiramate 25 mg bid (twice a day) Week 3: topiramate 25 mg q am (every day before noon) + topiramate 50 mg qhs Week 4: topiramate 50 mg bid Only one dosage adjustment (increase or decrease), based on efficacy or tolerability, may be made at the investigator's discretion. Subjects must maintain a dose of at least 50 mg/day to remain in the Treatment Period.&#xD;
onabotulinumtoxinA: All subjects will receive a minimum dose of 155 U Botulinum Toxin Type A Purified Neurotoxin Complex administered at 31 fixed-site, fixed-dose injections across seven (7) specific head/neck muscle areas at Visits 2-5.</description>
        </group>
        <group group_id="P2">
          <title>OnabotulinumtoxinA + Placebo</title>
          <description>Subject will receive 155 U onabotulinumtoxinA injections at 31 sites every 3 months for 12 months and treat daily with placebo. During the first month of the treatment period, subjects will titrate as follows:&#xD;
Week 1: 1 tab qhs (every night at bedtime) Week 2: 1 tab bid (twice daily) Week 3: 1 tab q am (every day before noon) + 2 tabs qhs Week 4: 2 tabs bid&#xD;
onabotulinumtoxinA: All subjects will receive a minimum dose of 155 U Botulinum Toxin Type A Purified Neurotoxin Complex administered at 31 fixed-site, fixed-dose injections across seven (7) specific head/neck muscle areas at Visits 2-5.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="10"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Only those subjects which randomized were included in the baseline analysis.</population>
      <group_list>
        <group group_id="B1">
          <title>OnabotulinumtoxinA + Topiramate</title>
          <description>Subject will receive 155 U onabotulinumtoxinA injections at 31 sites every 3 months for 12 months and treat daily with topiramate. During the first month of the treatment period, subjects will titrate as follows:&#xD;
Week 1: topiramate 25 mg qhs Week 2: topiramate 25 mg bid Week 3: topiramate 25 mg q am + topiramate 50 mg qhs Week 4: topiramate 50 mg bid Only one dosage adjustment (increase or decrease), based on efficacy or tolerability, may be made at the investigator's discretion. Subjects must maintain a dose of at least 50 mg/day to remain in the Treatment Period.&#xD;
onabotulinumtoxinA: All subjects will receive a minimum dose of 155 U Botulinum Toxin Type A Purified Neurotoxin Complex administered at 31 fixed-site, fixed-dose injections across seven (7) specific head/neck muscle areas at Visits 2-5.</description>
        </group>
        <group group_id="B2">
          <title>OnabotulinumtoxinA + Placebo</title>
          <description>Subject will receive 155 U onabotulinumtoxinA injections at 31 sites every 3 months for 12 months and treat daily with placebo. During the first month of the treatment period, subjects will titrate as follows:&#xD;
Week 1: 1 tab qhs Week 2: 1 tab bid Week 3: 1 tab q am + 2 tabs qhs Week 4: 2 tabs bid&#xD;
onabotulinumtoxinA: All subjects will receive a minimum dose of 155 U Botulinum Toxin Type A Purified Neurotoxin Complex administered at 31 fixed-site, fixed-dose injections across seven (7) specific head/neck muscle areas at Visits 2-5.</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="10"/>
            <count group_id="B2" value="10"/>
            <count group_id="B3" value="20"/>
          </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="40.84" spread="15.98"/>
                    <measurement group_id="B2" value="39.51" spread="6.99"/>
                    <measurement group_id="B3" value="40.18" spread="12.02"/>
                  </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="9"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="19"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="19"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Subject Attrition Post Randomization</title>
        <description>Count of subject attrition following randomization and reason for attrition (Consent withdrawn, Withdrawn due to adverse event, Lost to follow up)</description>
        <time_frame>Collected on Visit 2 (Day 29) through Visit 6 (Day 365)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>OnabotulinumtoxinA + Topiramate</title>
            <description>Subject will receive 155 U onabotulinumtoxinA injections at 31 sites every 3 months for 12 months and treat daily with topiramate. During the first month of the treatment period, subjects will titrate as follows:&#xD;
Week 1: topiramate 25 mg qhs Week 2: topiramate 25 mg bid Week 3: topiramate 25 mg q am + topiramate 50 mg qhs Week 4: topiramate 50 mg bid Only one dosage adjustment (increase or decrease), based on efficacy or tolerability, may be made at the investigator's discretion. Subjects must maintain a dose of at least 50 mg/day to remain in the Treatment Period.&#xD;
onabotulinumtoxinA: All subjects will receive a minimum dose of 155 U Botulinum Toxin Type A Purified Neurotoxin Complex administered at 31 fixed-site, fixed-dose injections across seven (7) specific head/neck muscle areas at Visits 2-5.</description>
          </group>
          <group group_id="O2">
            <title>OnabotulinumtoxinA + Placebo</title>
            <description>Subject will receive 155 U onabotulinumtoxinA injections at 31 sites every 3 months for 12 months and treat daily with placebo. During the first month of the treatment period, subjects will titrate as follows:&#xD;
Week 1: 1 tab qhs Week 2: 1 tab bid Week 3: 1 tab q am + 2 tabs qhs Week 4: 2 tabs bid&#xD;
onabotulinumtoxinA: All subjects will receive a minimum dose of 155 U Botulinum Toxin Type A Purified Neurotoxin Complex administered at 31 fixed-site, fixed-dose injections across seven (7) specific head/neck muscle areas at Visits 2-5.</description>
          </group>
        </group_list>
        <measure>
          <title>Subject Attrition Post Randomization</title>
          <description>Count of subject attrition following randomization and reason for attrition (Consent withdrawn, Withdrawn due to adverse event, Lost to follow up)</description>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Consent Withdrawn</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Withdrawn Due to Adverse Event</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Lost to Follow Up</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Subject Global Impression of Change (SGIC)</title>
        <description>Score on Subject Global Impression of Change at Visits 3-6 (Day 113 and 365). Likert scale ranging from 1-7, where 1 = extremely worse and 7 = extremely better.</description>
        <time_frame>Collected on Visit 3 (Day 113), Visit 4 (Day 197), Visit 5 (281), and Visit 6 (Day 365)</time_frame>
        <population>Number of participants vary at each visit based on the number of those still enrolled in the study at the time of the visit.</population>
        <group_list>
          <group group_id="O1">
            <title>OnabotulinumtoxinA + Topiramate</title>
            <description>Subject will receive 155 U onabotulinumtoxinA injections at 31 sites every 3 months for 12 months and treat daily with topiramate. During the first month of the treatment period, subjects will titrate as follows:&#xD;
Week 1: topiramate 25 mg q hs Week 2: topiramate 25 mg bid Week 3: topiramate 25 mg q am + topiramate 50mg q hs Week 4: topiramate 50mg bid Only one dosage adjustment (increase or decrease), based on efficacy or tolerability, may be made at the investigator's discretion. Subjects must maintain a dose of at least 50 mg/day to remain in the Treatment Period.&#xD;
onabotulinumtoxinA: All subjects will receive a minimum dose of 155 U Botulinum Toxin Type A Purified Neurotoxin Complex administered at 31 fixed-site, fixed-dose injections across seven (7) specific head/neck muscle areas at Visits 2-5.</description>
          </group>
          <group group_id="O2">
            <title>OnabotulinumtoxinA + Placebo</title>
            <description>Subject will receive 155 U onabotulinumtoxinA injections at 31 sites every 3 months for 12 months and treat daily with placebo. During the first month of the treatment period, subjects will titrate as follows:&#xD;
Week 1: 1 tab q hs Week 2: 1 tab bid Week 3: 1 tab q am + 2 tabs q hs Week 4: 2 tabs bid&#xD;
onabotulinumtoxinA: All subjects will receive a minimum dose of 155 U Botulinum Toxin Type A Purified Neurotoxin Complex administered at 31 fixed-site, fixed-dose injections across seven (7) specific head/neck muscle areas at Visits 2-5.</description>
          </group>
        </group_list>
        <measure>
          <title>Subject Global Impression of Change (SGIC)</title>
          <description>Score on Subject Global Impression of Change at Visits 3-6 (Day 113 and 365). Likert scale ranging from 1-7, where 1 = extremely worse and 7 = extremely better.</description>
          <population>Number of participants vary at each visit based on the number of those still enrolled in the study at the time of the visit.</population>
          <units>units 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="8"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Visit 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.38" spread="1.19"/>
                    <measurement group_id="O2" value="5.30" spread="1.25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visit 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="9"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.33" spread="0.82"/>
                    <measurement group_id="O2" value="5.77" spread="1.09"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visit 5</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.66" spread="0.52"/>
                    <measurement group_id="O2" value="6.17" spread="1.17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visit 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.00" spread="0.00"/>
                    <measurement group_id="O2" value="6.00" spread="1.26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Physician Global Impression of Change (PGIC)</title>
        <description>Score on Physician Global Impression of Change at Visits 3-6 (Day 113 and 365). Likert scale ranging from 1-7, where 1 = extremely worse and 7 = extremely better.</description>
        <time_frame>Collected on Visit 3 (Day 113), Visit 4 (Day 197), Visit 5 (281), and Visit 6 (Day 365)</time_frame>
        <population>Number of participants vary at each visit based on the number of those still enrolled in the study at the time of the visit.</population>
        <group_list>
          <group group_id="O1">
            <title>OnabotulinumtoxinA + Topiramate</title>
            <description>Subject will receive 155 U onabotulinumtoxinA injections at 31 sites every 3 months for 12 months and treat daily with topiramate. During the first month of the treatment period, subjects will titrate as follows:&#xD;
Week 1: topiramate 25 mg q hs Week 2: topiramate 25 mg bid Week 3: topiramate 25 mg q am + topiramate 50mg q hs Week 4: topiramate 50mg bid Only one dosage adjustment (increase or decrease), based on efficacy or tolerability, may be made at the investigator's discretion. Subjects must maintain a dose of at least 50 mg/day to remain in the Treatment Period.&#xD;
onabotulinumtoxinA: All subjects will receive a minimum dose of 155 U Botulinum Toxin Type A Purified Neurotoxin Complex administered at 31 fixed-site, fixed-dose injections across seven (7) specific head/neck muscle areas at Visits 2-5.</description>
          </group>
          <group group_id="O2">
            <title>OnabotulinumtoxinA + Placebo</title>
            <description>Subject will receive 155 U onabotulinumtoxinA injections at 31 sites every 3 months for 12 months and treat daily with placebo. During the first month of the treatment period, subjects will titrate as follows:&#xD;
Week 1: 1 tab q hs Week 2: 1 tab bid Week 3: 1 tab q am + 2 tabs q hs Week 4: 2 tabs bid&#xD;
onabotulinumtoxinA: All subjects will receive a minimum dose of 155 U Botulinum Toxin Type A Purified Neurotoxin Complex administered at 31 fixed-site, fixed-dose injections across seven (7) specific head/neck muscle areas at Visits 2-5.</description>
          </group>
        </group_list>
        <measure>
          <title>Physician Global Impression of Change (PGIC)</title>
          <description>Score on Physician Global Impression of Change at Visits 3-6 (Day 113 and 365). Likert scale ranging from 1-7, where 1 = extremely worse and 7 = extremely better.</description>
          <population>Number of participants vary at each visit based on the number of those still enrolled in the study at the time of the visit.</population>
          <units>units 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="8"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Visit 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.25" spread="1.16"/>
                    <measurement group_id="O2" value="5.30" spread="1.25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visit 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="9"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.40" spread="1.34"/>
                    <measurement group_id="O2" value="5.89" spread="0.93"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visit 5</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.67" spread="0.52"/>
                    <measurement group_id="O2" value="5.83" spread="1.94"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visit 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.83" spread="0.41"/>
                    <measurement group_id="O2" value="5.83" spread="1.47"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Subject's Controlled Oral Word Association Test (COWAT) Score Percent Change Compared From Baseline to Visits 3-6</title>
        <description>The Controlled Oral Word Association Test (COWAT) is a measure of verbal fluency. Raw COWAT scores have a lower bound of 0 with no upper bound. Higher scores indicate better verbal fluency. COWAT score percent change from baseline will be reported. Positive change scores represent better verbal fluency compared to baseline.</description>
        <time_frame>Baseline, Visit 3 (Day 113) through Visit 6 (Day 365)</time_frame>
        <population>Number of participants vary at each visit based on the number of those still enrolled in the study at the time of the visit.</population>
        <group_list>
          <group group_id="O1">
            <title>OnabotulinumtoxinA + Topiramate</title>
            <description>Subject will receive 155 U onabotulinumtoxinA injections at 31 sites every 3 months for 12 months and treat daily with topiramate. During the first month of the treatment period, subjects will titrate as follows:&#xD;
Week 1: topiramate 25 mg qhs Week 2: topiramate 25 mg bid Week 3: topiramate 25 mg q am + topiramate 50 mg qhs Week 4: topiramate 50 mg bid Only one dosage adjustment (increase or decrease), based on efficacy or tolerability, may be made at the investigator's discretion. Subjects must maintain a dose of at least 50 mg/day to remain in the Treatment Period.&#xD;
onabotulinumtoxinA: All subjects will receive a minimum dose of 155 U Botulinum Toxin Type A Purified Neurotoxin Complex administered at 31 fixed-site, fixed-dose injections across seven (7) specific head/neck muscle areas at Visits 2-5.&#xD;
Topiramate: Subjects randomized to the onabotulinumtoxinA + topiramate group will receive:&#xD;
Week 1: topiramate 25 mg qhs Week 2: topiramate 25 mg bid Week 3: topiramate</description>
          </group>
          <group group_id="O2">
            <title>OnabotulinumtoxinA + Placebo</title>
            <description>Subject will receive 155 U onabotulinumtoxinA injections at 31 sites every 3 months for 12 months and treat daily with placebo. During the first month of the treatment period, subjects will titrate as follows:&#xD;
Week 1: 1 tab qhs Week 2: 1 tab bid Week 3: 1 tab q am + 2 tabs qhs Week 4: 2 tabs bid&#xD;
onabotulinumtoxinA: All subjects will receive a minimum dose of 155 U Botulinum Toxin Type A Purified Neurotoxin Complex administered at 31 fixed-site, fixed-dose injections across seven (7) specific head/neck muscle areas at Visits 2-5.&#xD;
Placebo: Subjects randomized to the onabotulinumtoxinA + placebo group will receive:&#xD;
Week 1: placebo 25 mg qhs Week 2: placebo 25 mg bid Week 3: placebo 25 mg q am + placebo 50 mg qhs Week 4: placebo 50 mg bid Only one dosage adjustment (increase or decrease), based on efficacy or tolerability, may be made at the investigator's discretion. Subjects must maintain a dose of at least 50 mg/day to remain in the Treatment Period.</description>
          </group>
        </group_list>
        <measure>
          <title>Subject's Controlled Oral Word Association Test (COWAT) Score Percent Change Compared From Baseline to Visits 3-6</title>
          <description>The Controlled Oral Word Association Test (COWAT) is a measure of verbal fluency. Raw COWAT scores have a lower bound of 0 with no upper bound. Higher scores indicate better verbal fluency. COWAT score percent change from baseline will be reported. Positive change scores represent better verbal fluency compared to baseline.</description>
          <population>Number of participants vary at each visit based on the number of those still enrolled in the study at the time of the visit.</population>
          <units>percentage of change from baseline score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Visit 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-17.06" spread="9.47"/>
                    <measurement group_id="O2" value="-3.50" spread="23.71"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visit 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="9"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-17.93" spread="10.63"/>
                    <measurement group_id="O2" value="-8.93" spread="22.95"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visit 5</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-12.63" spread="12.24"/>
                    <measurement group_id="O2" value="1.48" spread="17.32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visit 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-5.05" spread="20.99"/>
                    <measurement group_id="O2" value="-4.99" spread="19.04"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Headache Days</title>
        <description>Number of Headache Days reported in 30-day Baseline Period and Treatment Period Months 1-12</description>
        <time_frame>Baseline and Months 1-12</time_frame>
        <population>Number of participants vary at each visit based on the number of those still enrolled in the study at the time of the visit.</population>
        <group_list>
          <group group_id="O1">
            <title>OnabotulinumtoxinA + Topiramate</title>
            <description>Subject will receive 155 U onabotulinumtoxinA injections at 31 sites every 3 months for 12 months and treat daily with topiramate. During the first month of the treatment period, subjects will titrate as follows:&#xD;
Week 1: topiramate 25 mg qhs Week 2: topiramate 25 mg bid Week 3: topiramate 25 mg q am + topiramate 50 mg qhs Week 4: topiramate 50 mg bid Only one dosage adjustment (increase or decrease), based on efficacy or tolerability, may be made at the investigator's discretion. Subjects must maintain a dose of at least 50 mg/day to remain in the Treatment Period.&#xD;
onabotulinumtoxinA: All subjects will receive a minimum dose of 155 U Botulinum Toxin Type A Purified Neurotoxin Complex administered at 31 fixed-site, fixed-dose injections across seven (7) specific head/neck muscle areas at Visits 2-5.&#xD;
Topiramate: Subjects randomized to the onabotulinumtoxinA + topiramate group will receive:&#xD;
Week 1: topiramate 25 mg qhs Week 2: topiramate 25 mg bid Week 3: topiramate</description>
          </group>
          <group group_id="O2">
            <title>OnabotulinumtoxinA + Placebo</title>
            <description>Subject will receive 155 U onabotulinumtoxinA injections at 31 sites every 3 months for 12 months and treat daily with placebo. During the first month of the treatment period, subjects will titrate as follows:&#xD;
Week 1: 1 tab qhs Week 2: 1 tab bid Week 3: 1 tab q am + 2 tabs qhs Week 4: 2 tabs bid&#xD;
onabotulinumtoxinA: All subjects will receive a minimum dose of 155 U Botulinum Toxin Type A Purified Neurotoxin Complex administered at 31 fixed-site, fixed-dose injections across seven (7) specific head/neck muscle areas at Visits 2-5.&#xD;
Placebo: Subjects randomized to the onabotulinumtoxinA + placebo group will receive:&#xD;
Week 1: placebo 25 mg qhs Week 2: placebo 25 mg bid Week 3: placebo 25 mg q am + placebo 50 mg qhs Week 4: placebo 50 mg bid Only one dosage adjustment (increase or decrease), based on efficacy or tolerability, may be made at the investigator's discretion. Subjects must maintain a dose of at least 50 mg/day to remain in the Treatment Period.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Headache Days</title>
          <description>Number of Headache Days reported in 30-day Baseline Period and Treatment Period Months 1-12</description>
          <population>Number of participants vary at each visit based on the number of those still enrolled in the study at the time of the visit.</population>
          <units>Headache days</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="10"/>
              </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="10"/>
                    <count group_id="O2" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22.95" spread="4.39"/>
                    <measurement group_id="O2" value="23.77" spread="4.64"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="9"/>
                    <count group_id="O2" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18.41" spread="5.96"/>
                    <measurement group_id="O2" value="21.67" spread="4.28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16.50" spread="7.61"/>
                    <measurement group_id="O2" value="17.54" spread="6.81"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16.83" spread="7.12"/>
                    <measurement group_id="O2" value="18.37" spread="7.76"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="9"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15.74" spread="8.09"/>
                    <measurement group_id="O2" value="14.39" spread="10.05"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 5</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="9"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.34" spread="7.17"/>
                    <measurement group_id="O2" value="13.47" spread="8.95"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="9"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15.18" spread="6.07"/>
                    <measurement group_id="O2" value="16.58" spread="7.68"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="8"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.64" spread="6.39"/>
                    <measurement group_id="O2" value="12.54" spread="9.23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 8</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.36" spread="5.16"/>
                    <measurement group_id="O2" value="11.5" spread="7.26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 9</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.02" spread="5.6"/>
                    <measurement group_id="O2" value="9.96" spread="5.71"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 10</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.93" spread="4.59"/>
                    <measurement group_id="O2" value="8.02" spread="1.06"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 11</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                    <count group_id="O2" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.36" spread="6.5"/>
                    <measurement group_id="O2" value="8.51" spread="6.09"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                    <count group_id="O2" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.51" spread="5.04"/>
                    <measurement group_id="O2" value="8.06" spread="5.34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Headache Impact Test (HIT-6) Scores at Visits 2-6 to Measure Effect of Headache in Subject's Life</title>
        <description>The Headache Impact Test (HIT-6) is a tool used to measure the impact headaches have on an individual's ability to function on the job, at school, at home and in social situations. The HIT-6 score range is from 36 to 78 with higher scores indicating greater impact (worse outcome).</description>
        <time_frame>Collected on Visit 2 (Day 29), 3 (Day 113), Visit 4 (Day 197), Visit 5 (281), and Visit 6 (Day 365)</time_frame>
        <population>Number of participants vary at each visit based on the number of those still enrolled in the study at the time of the visit.</population>
        <group_list>
          <group group_id="O1">
            <title>OnabotulinumtoxinA + Topiramate</title>
            <description>Subject will receive 155 U onabotulinumtoxinA injections at 31 sites every 3 months for 12 months and treat daily with topiramate. During the first month of the treatment period, subjects will titrate as follows:&#xD;
Week 1: topiramate 25 mg qhs Week 2: topiramate 25 mg bid Week 3: topiramate 25 mg q am + topiramate 50 mg qhs Week 4: topiramate 50 mg bid Only one dosage adjustment (increase or decrease), based on efficacy or tolerability, may be made at the investigator's discretion. Subjects must maintain a dose of at least 50 mg/day to remain in the Treatment Period.&#xD;
onabotulinumtoxinA: All subjects will receive a minimum dose of 155 U Botulinum Toxin Type A Purified Neurotoxin Complex administered at 31 fixed-site, fixed-dose injections across seven (7) specific head/neck muscle areas at Visits 2-5.&#xD;
Topiramate: Subjects randomized to the onabotulinumtoxinA + topiramate group will receive:&#xD;
Week 1: topiramate 25 mg qhs Week 2: topiramate 25 mg bid Week 3: topiramate</description>
          </group>
          <group group_id="O2">
            <title>OnabotulinumtoxinA + Placebo</title>
            <description>Subject will receive 155 U onabotulinumtoxinA injections at 31 sites every 3 months for 12 months and treat daily with placebo. During the first month of the treatment period, subjects will titrate as follows:&#xD;
Week 1: 1 tab qhs Week 2: 1 tab bid Week 3: 1 tab q am + 2 tabs qhs Week 4: 2 tabs bid&#xD;
onabotulinumtoxinA: All subjects will receive a minimum dose of 155 U Botulinum Toxin Type A Purified Neurotoxin Complex administered at 31 fixed-site, fixed-dose injections across seven (7) specific head/neck muscle areas at Visits 2-5.&#xD;
Placebo: Subjects randomized to the onabotulinumtoxinA + placebo group will receive:&#xD;
Week 1: placebo 25 mg qhs Week 2: placebo 25 mg bid Week 3: placebo 25 mg q am + placebo 50 mg qhs Week 4: placebo 50 mg bid Only one dosage adjustment (increase or decrease), based on efficacy or tolerability, may be made at the investigator's discretion. Subjects must maintain a dose of at least 50 mg/day to remain in the Treatment Period.</description>
          </group>
        </group_list>
        <measure>
          <title>Headache Impact Test (HIT-6) Scores at Visits 2-6 to Measure Effect of Headache in Subject's Life</title>
          <description>The Headache Impact Test (HIT-6) is a tool used to measure the impact headaches have on an individual's ability to function on the job, at school, at home and in social situations. The HIT-6 score range is from 36 to 78 with higher scores indicating greater impact (worse outcome).</description>
          <population>Number of participants vary at each visit based on the number of those still enrolled in the study at the time of the visit.</population>
          <units>units 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="10"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Visit 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                    <count group_id="O2" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="66.40" spread="5.19"/>
                    <measurement group_id="O2" value="66.50" spread="3.84"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visit 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="9"/>
                    <count group_id="O2" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="61.89" spread="6.92"/>
                    <measurement group_id="O2" value="59.9" spread="7.77"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visit 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="54.5" spread="5.39"/>
                    <measurement group_id="O2" value="60.44" spread="8.19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visit 5</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="9"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="52.83" spread="7.44"/>
                    <measurement group_id="O2" value="58.71" spread="7.85"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visit 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="52.57" spread="7.20"/>
                    <measurement group_id="O2" value="54.17" spread="9.81"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>MEWT Simple Reaction Time Sub-test Score Percent Change Compared From Baseline to Visits 3-6</title>
        <description>The Mental Efficiency Workload Test (MEWT) is a cognitive functioning scale with four sub-scales (Simple Reaction Time, Running Memory Continuous Performance Task, Matching to Sample, and Mathematical Processing). Each sub-scale has a minimum and maximum values of 1 to 10, 1 indicates the poorest level and 10 indicates the best level of cognitive functioning. MEWT sub-scale score percent change from baseline will be reported. Positive change scores represent better cognitive functioning compared to baseline.</description>
        <time_frame>Baseline, Visit 3 (Day 113), Visit 4 (Day 197), Visit 5 (281), and Visit 6 (Day 365)</time_frame>
        <population>Number of participants vary at each visit based on the number of those still enrolled in the study at the time of the visit.</population>
        <group_list>
          <group group_id="O1">
            <title>OnabotulinumtoxinA + Topiramate</title>
            <description>Subject will receive 155 U onabotulinumtoxinA injections at 31 sites every 3 months for 12 months and treat daily with topiramate. During the first month of the treatment period, subjects will titrate as follows:&#xD;
Week 1: topiramate 25 mg qhs Week 2: topiramate 25 mg bid Week 3: topiramate 25 mg q am + topiramate 50 mg qhs Week 4: topiramate 50 mg bid Only one dosage adjustment (increase or decrease), based on efficacy or tolerability, may be made at the investigator's discretion. Subjects must maintain a dose of at least 50 mg/day to remain in the Treatment Period.&#xD;
onabotulinumtoxinA: All subjects will receive a minimum dose of 155 U Botulinum Toxin Type A Purified Neurotoxin Complex administered at 31 fixed-site, fixed-dose injections across seven (7) specific head/neck muscle areas at Visits 2-5.&#xD;
Topiramate: Subjects randomized to the onabotulinumtoxinA + topiramate group will receive:&#xD;
Week 1: topiramate 25 mg qhs Week 2: topiramate 25 mg bid Week 3: topiramate</description>
          </group>
          <group group_id="O2">
            <title>OnabotulinumtoxinA + Placebo</title>
            <description>Subject will receive 155 U onabotulinumtoxinA injections at 31 sites every 3 months for 12 months and treat daily with placebo. During the first month of the treatment period, subjects will titrate as follows:&#xD;
Week 1: 1 tab qhs Week 2: 1 tab bid Week 3: 1 tab q am + 2 tabs qhs Week 4: 2 tabs bid&#xD;
onabotulinumtoxinA: All subjects will receive a minimum dose of 155 U Botulinum Toxin Type A Purified Neurotoxin Complex administered at 31 fixed-site, fixed-dose injections across seven (7) specific head/neck muscle areas at Visits 2-5.&#xD;
Placebo: Subjects randomized to the onabotulinumtoxinA + placebo group will receive:&#xD;
Week 1: placebo 25 mg qhs Week 2: placebo 25 mg bid Week 3: placebo 25 mg q am + placebo 50 mg qhs Week 4: placebo 50 mg bid Only one dosage adjustment (increase or decrease), based on efficacy or tolerability, may be made at the investigator's discretion. Subjects must maintain a dose of at least 50 mg/day to remain in the Treatment Period.</description>
          </group>
        </group_list>
        <measure>
          <title>MEWT Simple Reaction Time Sub-test Score Percent Change Compared From Baseline to Visits 3-6</title>
          <description>The Mental Efficiency Workload Test (MEWT) is a cognitive functioning scale with four sub-scales (Simple Reaction Time, Running Memory Continuous Performance Task, Matching to Sample, and Mathematical Processing). Each sub-scale has a minimum and maximum values of 1 to 10, 1 indicates the poorest level and 10 indicates the best level of cognitive functioning. MEWT sub-scale score percent change from baseline will be reported. Positive change scores represent better cognitive functioning compared to baseline.</description>
          <population>Number of participants vary at each visit based on the number of those still enrolled in the study at the time of the visit.</population>
          <units>percentage of change from baseline score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Visit 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-8.90" spread="18.62"/>
                    <measurement group_id="O2" value="14.22" spread="30.32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visit 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="9"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.20" spread="17.15"/>
                    <measurement group_id="O2" value="4.76" spread="8.44"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visit 5</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.87" spread="25.48"/>
                    <measurement group_id="O2" value="-4.17" spread="10.05"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visit 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.16" spread="24.15"/>
                    <measurement group_id="O2" value="2.31" spread="18.86"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>MEWT Running Memory Continuous Performance Task Sub-test Score Percent Change Compared From Baseline to Visits 3-6</title>
        <description>The Mental Efficiency Workload Test (MEWT) is a cognitive functioning scale with four sub-scales (Simple Reaction Time, Running Memory Continuous Performance Task, Matching to Sample, and Mathematical Processing). Each sub-scale has a minimum and maximum values of 1 to 10, 1 indicates the poorest level and 10 indicates the best level of cognitive functioning. MEWT sub-scale score percent change from baseline will be reported. Positive change scores represent better cognitive functioning compared to baseline.</description>
        <time_frame>Baseline, Visit 3 (Day 113), Visit 4 (Day 197), Visit 5 (281), and Visit 6 (Day 365)</time_frame>
        <population>Number of participants vary at each visit based on the number of those still enrolled in the study at the time of the visit.</population>
        <group_list>
          <group group_id="O1">
            <title>OnabotulinumtoxinA + Topiramate</title>
            <description>Subject will receive 155 U onabotulinumtoxinA injections at 31 sites every 3 months for 12 months and treat daily with topiramate. During the first month of the treatment period, subjects will titrate as follows:&#xD;
Week 1: topiramate 25 mg qhs Week 2: topiramate 25 mg bid Week 3: topiramate 25 mg q am + topiramate 50 mg qhs Week 4: topiramate 50 mg bid Only one dosage adjustment (increase or decrease), based on efficacy or tolerability, may be made at the investigator's discretion. Subjects must maintain a dose of at least 50 mg/day to remain in the Treatment Period.&#xD;
onabotulinumtoxinA: All subjects will receive a minimum dose of 155 U Botulinum Toxin Type A Purified Neurotoxin Complex administered at 31 fixed-site, fixed-dose injections across seven (7) specific head/neck muscle areas at Visits 2-5.&#xD;
Topiramate: Subjects randomized to the onabotulinumtoxinA + topiramate group will receive:&#xD;
Week 1: topiramate 25 mg qhs Week 2: topiramate 25 mg bid Week 3: topiramate</description>
          </group>
          <group group_id="O2">
            <title>OnabotulinumtoxinA + Placebo</title>
            <description>Subject will receive 155 U onabotulinumtoxinA injections at 31 sites every 3 months for 12 months and treat daily with placebo. During the first month of the treatment period, subjects will titrate as follows:&#xD;
Week 1: 1 tab qhs Week 2: 1 tab bid Week 3: 1 tab q am + 2 tabs qhs Week 4: 2 tabs bid&#xD;
onabotulinumtoxinA: All subjects will receive a minimum dose of 155 U Botulinum Toxin Type A Purified Neurotoxin Complex administered at 31 fixed-site, fixed-dose injections across seven (7) specific head/neck muscle areas at Visits 2-5.&#xD;
Placebo: Subjects randomized to the onabotulinumtoxinA + placebo group will receive:&#xD;
Week 1: placebo 25 mg qhs Week 2: placebo 25 mg bid Week 3: placebo 25 mg q am + placebo 50 mg qhs Week 4: placebo 50 mg bid Only one dosage adjustment (increase or decrease), based on efficacy or tolerability, may be made at the investigator's discretion. Subjects must maintain a dose of at least 50 mg/day to remain in the Treatment Period.</description>
          </group>
        </group_list>
        <measure>
          <title>MEWT Running Memory Continuous Performance Task Sub-test Score Percent Change Compared From Baseline to Visits 3-6</title>
          <description>The Mental Efficiency Workload Test (MEWT) is a cognitive functioning scale with four sub-scales (Simple Reaction Time, Running Memory Continuous Performance Task, Matching to Sample, and Mathematical Processing). Each sub-scale has a minimum and maximum values of 1 to 10, 1 indicates the poorest level and 10 indicates the best level of cognitive functioning. MEWT sub-scale score percent change from baseline will be reported. Positive change scores represent better cognitive functioning compared to baseline.</description>
          <population>Number of participants vary at each visit based on the number of those still enrolled in the study at the time of the visit.</population>
          <units>percentage of change from baseline score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Visit 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-15.66" spread="38.87"/>
                    <measurement group_id="O2" value="1.13" spread="24.70"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visit 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="9"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.20" spread="41.31"/>
                    <measurement group_id="O2" value="4.39" spread="16.55"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visit 5</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.96" spread="43.64"/>
                    <measurement group_id="O2" value="18.81" spread="28.45"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visit 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-6.99" spread="43.50"/>
                    <measurement group_id="O2" value="2.2" spread="31.91"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>MEWT Matching to Sample Sub-test Score Percent Change Compared From Baseline to Visits 3-6</title>
        <description>The Mental Efficiency Workload Test (MEWT) is a cognitive functioning scale with four sub-scales (Simple Reaction Time, Running Memory Continuous Performance Task, Matching to Sample, and Mathematical Processing). Each sub-scale has a minimum and maximum values of 1 to 10, 1 indicates the poorest level and 10 indicates the best level of cognitive functioning. MEWT sub-scale score percent change from baseline will be reported. Positive change scores represent better cognitive functioning compared to baseline.</description>
        <time_frame>Baseline, Visit 3 (Day 113), Visit 4 (Day 197), Visit 5 (281), and Visit 6 (Day 365)</time_frame>
        <population>Number of participants vary at each visit based on the number of those still enrolled in the study at the time of the visit.</population>
        <group_list>
          <group group_id="O1">
            <title>OnabotulinumtoxinA + Topiramate</title>
            <description>Subject will receive 155 U onabotulinumtoxinA injections at 31 sites every 3 months for 12 months and treat daily with topiramate. During the first month of the treatment period, subjects will titrate as follows:&#xD;
Week 1: topiramate 25 mg qhs Week 2: topiramate 25 mg bid Week 3: topiramate 25 mg q am + topiramate 50 mg qhs Week 4: topiramate 50 mg bid Only one dosage adjustment (increase or decrease), based on efficacy or tolerability, may be made at the investigator's discretion. Subjects must maintain a dose of at least 50 mg/day to remain in the Treatment Period.&#xD;
onabotulinumtoxinA: All subjects will receive a minimum dose of 155 U Botulinum Toxin Type A Purified Neurotoxin Complex administered at 31 fixed-site, fixed-dose injections across seven (7) specific head/neck muscle areas at Visits 2-5.&#xD;
Topiramate: Subjects randomized to the onabotulinumtoxinA + topiramate group will receive:&#xD;
Week 1: topiramate 25 mg qhs Week 2: topiramate 25 mg bid Week 3: topiramate</description>
          </group>
          <group group_id="O2">
            <title>OnabotulinumtoxinA + Placebo</title>
            <description>Subject will receive 155 U onabotulinumtoxinA injections at 31 sites every 3 months for 12 months and treat daily with placebo. During the first month of the treatment period, subjects will titrate as follows:&#xD;
Week 1: 1 tab qhs Week 2: 1 tab bid Week 3: 1 tab q am + 2 tabs qhs Week 4: 2 tabs bid&#xD;
onabotulinumtoxinA: All subjects will receive a minimum dose of 155 U Botulinum Toxin Type A Purified Neurotoxin Complex administered at 31 fixed-site, fixed-dose injections across seven (7) specific head/neck muscle areas at Visits 2-5.&#xD;
Placebo: Subjects randomized to the onabotulinumtoxinA + placebo group will receive:&#xD;
Week 1: placebo 25 mg qhs Week 2: placebo 25 mg bid Week 3: placebo 25 mg q am + placebo 50 mg qhs Week 4: placebo 50 mg bid Only one dosage adjustment (increase or decrease), based on efficacy or tolerability, may be made at the investigator's discretion. Subjects must maintain a dose of at least 50 mg/day to remain in the Treatment Period.</description>
          </group>
        </group_list>
        <measure>
          <title>MEWT Matching to Sample Sub-test Score Percent Change Compared From Baseline to Visits 3-6</title>
          <description>The Mental Efficiency Workload Test (MEWT) is a cognitive functioning scale with four sub-scales (Simple Reaction Time, Running Memory Continuous Performance Task, Matching to Sample, and Mathematical Processing). Each sub-scale has a minimum and maximum values of 1 to 10, 1 indicates the poorest level and 10 indicates the best level of cognitive functioning. MEWT sub-scale score percent change from baseline will be reported. Positive change scores represent better cognitive functioning compared to baseline.</description>
          <population>Number of participants vary at each visit based on the number of those still enrolled in the study at the time of the visit.</population>
          <units>percentage of change from baseline score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Visit 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19.06" spread="44.13"/>
                    <measurement group_id="O2" value="21.74" spread="27.86"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visit 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="9"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15.04" spread="47.59"/>
                    <measurement group_id="O2" value="8.59" spread="25.34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visit 5</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18.49" spread="45.11"/>
                    <measurement group_id="O2" value="12.72" spread="23.34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visit 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="40.86" spread="42.88"/>
                    <measurement group_id="O2" value="24.75" spread="49.32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>MEWT Mathematical Processing Sub-test Score Percent Change Compared From Baseline to Visits 3-6</title>
        <description>The Mental Efficiency Workload Test (MEWT) is a cognitive functioning scale with four sub-scales (Simple Reaction Time, Running Memory Continuous Performance Task, Matching to Sample, and Mathematical Processing). Each sub-scale has a minimum and maximum values of 1 to 10, 1 indicates the poorest level and 10 indicates the best level of cognitive functioning. MEWT sub-scale score percent change from baseline will be reported. Positive change scores represent better cognitive functioning compared to baseline.</description>
        <time_frame>Baseline, Visit 3 (Day 113), Visit 4 (Day 197), Visit 5 (281), and Visit 6 (Day 365)</time_frame>
        <population>Number of participants vary at each visit based on the number of those still enrolled in the study at the time of the visit.</population>
        <group_list>
          <group group_id="O1">
            <title>OnabotulinumtoxinA + Topiramate</title>
            <description>Subject will receive 155 U onabotulinumtoxinA injections at 31 sites every 3 months for 12 months and treat daily with topiramate. During the first month of the treatment period, subjects will titrate as follows:&#xD;
Week 1: topiramate 25 mg qhs Week 2: topiramate 25 mg bid Week 3: topiramate 25 mg q am + topiramate 50 mg qhs Week 4: topiramate 50 mg bid Only one dosage adjustment (increase or decrease), based on efficacy or tolerability, may be made at the investigator's discretion. Subjects must maintain a dose of at least 50 mg/day to remain in the Treatment Period.&#xD;
onabotulinumtoxinA: All subjects will receive a minimum dose of 155 U Botulinum Toxin Type A Purified Neurotoxin Complex administered at 31 fixed-site, fixed-dose injections across seven (7) specific head/neck muscle areas at Visits 2-5.&#xD;
Topiramate: Subjects randomized to the onabotulinumtoxinA + topiramate group will receive:&#xD;
Week 1: topiramate 25 mg qhs Week 2: topiramate 25 mg bid Week 3: topiramate</description>
          </group>
          <group group_id="O2">
            <title>OnabotulinumtoxinA + Placebo</title>
            <description>Subject will receive 155 U onabotulinumtoxinA injections at 31 sites every 3 months for 12 months and treat daily with placebo. During the first month of the treatment period, subjects will titrate as follows:&#xD;
Week 1: 1 tab qhs Week 2: 1 tab bid Week 3: 1 tab q am + 2 tabs qhs Week 4: 2 tabs bid&#xD;
onabotulinumtoxinA: All subjects will receive a minimum dose of 155 U Botulinum Toxin Type A Purified Neurotoxin Complex administered at 31 fixed-site, fixed-dose injections across seven (7) specific head/neck muscle areas at Visits 2-5.&#xD;
Placebo: Subjects randomized to the onabotulinumtoxinA + placebo group will receive:&#xD;
Week 1: placebo 25 mg qhs Week 2: placebo 25 mg bid Week 3: placebo 25 mg q am + placebo 50 mg qhs Week 4: placebo 50 mg bid Only one dosage adjustment (increase or decrease), based on efficacy or tolerability, may be made at the investigator's discretion. Subjects must maintain a dose of at least 50 mg/day to remain in the Treatment Period.</description>
          </group>
        </group_list>
        <measure>
          <title>MEWT Mathematical Processing Sub-test Score Percent Change Compared From Baseline to Visits 3-6</title>
          <description>The Mental Efficiency Workload Test (MEWT) is a cognitive functioning scale with four sub-scales (Simple Reaction Time, Running Memory Continuous Performance Task, Matching to Sample, and Mathematical Processing). Each sub-scale has a minimum and maximum values of 1 to 10, 1 indicates the poorest level and 10 indicates the best level of cognitive functioning. MEWT sub-scale score percent change from baseline will be reported. Positive change scores represent better cognitive functioning compared to baseline.</description>
          <population>Number of participants vary at each visit based on the number of those still enrolled in the study at the time of the visit.</population>
          <units>percentage of change from baseline score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Visit 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-11.23" spread="22.61"/>
                    <measurement group_id="O2" value="17.74" spread="50.54"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visit 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="9"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-22.90" spread="16.48"/>
                    <measurement group_id="O2" value="16.43" spread="35.88"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visit 5</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-23.81" spread="16.26"/>
                    <measurement group_id="O2" value="28.61" spread="48.44"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visit 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.52" spread="8.91"/>
                    <measurement group_id="O2" value="29.44" spread="50.47"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Subject Estimation of Compliance With Daily Study Drug</title>
        <description>Subject estimation of compliance with daily study drug during the study period. Compliance ranges from 0% to 100% with higher percentages indicating greater compliance with study drug.</description>
        <time_frame>Collected on Visit 2 (Day 29), 3 (Day 113), Visit 4 (Day 197), and Visit 5 (281)</time_frame>
        <population>Number of participants vary at each visit based on the number of those still enrolled in the study at the time of the visit.</population>
        <group_list>
          <group group_id="O1">
            <title>OnabotulinumtoxinA + Topiramate</title>
            <description>Subject will receive 155 U onabotulinumtoxinA injections at 31 sites every 3 months for 12 months and treat daily with topiramate. During the first month of the treatment period, subjects will titrate as follows:&#xD;
Week 1: topiramate 25 mg qhs Week 2: topiramate 25 mg bid Week 3: topiramate 25 mg q am + topiramate 50 mg qhs Week 4: topiramate 50 mg bid Only one dosage adjustment (increase or decrease), based on efficacy or tolerability, may be made at the investigator's discretion. Subjects must maintain a dose of at least 50 mg/day to remain in the Treatment Period.&#xD;
onabotulinumtoxinA: All subjects will receive a minimum dose of 155 U Botulinum Toxin Type A Purified Neurotoxin Complex administered at 31 fixed-site, fixed-dose injections across seven (7) specific head/neck muscle areas at Visits 2-5.&#xD;
Topiramate: Subjects randomized to the onabotulinumtoxinA + topiramate group will receive:&#xD;
Week 1: topiramate 25 mg qhs Week 2: topiramate 25 mg bid Week 3: topiramate</description>
          </group>
          <group group_id="O2">
            <title>OnabotulinumtoxinA + Placebo</title>
            <description>Subject will receive 155 U onabotulinumtoxinA injections at 31 sites every 3 months for 12 months and treat daily with placebo. During the first month of the treatment period, subjects will titrate as follows:&#xD;
Week 1: 1 tab qhs Week 2: 1 tab bid Week 3: 1 tab q am + 2 tabs qhs Week 4: 2 tabs bid&#xD;
onabotulinumtoxinA: All subjects will receive a minimum dose of 155 U Botulinum Toxin Type A Purified Neurotoxin Complex administered at 31 fixed-site, fixed-dose injections across seven (7) specific head/neck muscle areas at Visits 2-5.&#xD;
Placebo: Subjects randomized to the onabotulinumtoxinA + placebo group will receive:&#xD;
Week 1: placebo 25 mg qhs Week 2: placebo 25 mg bid Week 3: placebo 25 mg q am + placebo 50 mg qhs Week 4: placebo 50 mg bid Only one dosage adjustment (increase or decrease), based on efficacy or tolerability, may be made at the investigator's discretion. Subjects must maintain a dose of at least 50 mg/day to remain in the Treatment Period.</description>
          </group>
        </group_list>
        <measure>
          <title>Subject Estimation of Compliance With Daily Study Drug</title>
          <description>Subject estimation of compliance with daily study drug during the study period. Compliance ranges from 0% to 100% with higher percentages indicating greater compliance with study drug.</description>
          <population>Number of participants vary at each visit based on the number of those still enrolled in the study at the time of the visit.</population>
          <units>percentage of compliance</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Visit 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="9"/>
                    <count group_id="O2" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100" spread="0"/>
                    <measurement group_id="O2" value="99.73" spread="0.58"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visit 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="99.84" spread="0.46"/>
                    <measurement group_id="O2" value="99.73" spread="0.56"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visit 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="9"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="99.55" spread="1.10"/>
                    <measurement group_id="O2" value="97.65" spread="3.09"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visit 5</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="98.69" spread="1.61"/>
                    <measurement group_id="O2" value="99.63" spread="2.35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Non-Serious Adverse Events Between Groups</title>
        <time_frame>13 Months (Visit 1 to Visit 6)</time_frame>
        <population>All consenting participants.</population>
        <group_list>
          <group group_id="O1">
            <title>OnabotulinumtoxinA + Topiramate</title>
            <description>Subject will receive 155 U onabotulinumtoxinA injections at 31 sites every 3 months for 12 months and treat daily with topiramate. During the first month of the treatment period, subjects will titrate as follows:&#xD;
Week 1: topiramate 25 mg qhs Week 2: topiramate 25 mg bid Week 3: topiramate 25 mg q am + topiramate 50 mg qhs Week 4: topiramate 50 mg bid Only one dosage adjustment (increase or decrease), based on efficacy or tolerability, may be made at the investigator's discretion. Subjects must maintain a dose of at least 50 mg/day to remain in the Treatment Period.&#xD;
onabotulinumtoxinA: All subjects will receive a minimum dose of 155 U Botulinum Toxin Type A Purified Neurotoxin Complex administered at 31 fixed-site, fixed-dose injections across seven (7) specific head/neck muscle areas at Visits 2-5.&#xD;
Topiramate: Subjects randomized to the onabotulinumtoxinA + topiramate group will receive:&#xD;
Week 1: topiramate 25 mg qhs Week 2: topiramate 25 mg bid Week 3: topiramate</description>
          </group>
          <group group_id="O2">
            <title>OnabotulinumtoxinA + Placebo</title>
            <description>Subject will receive 155 U onabotulinumtoxinA injections at 31 sites every 3 months for 12 months and treat daily with placebo. During the first month of the treatment period, subjects will titrate as follows:&#xD;
Week 1: 1 tab qhs Week 2: 1 tab bid Week 3: 1 tab q am + 2 tabs qhs Week 4: 2 tabs bid&#xD;
onabotulinumtoxinA: All subjects will receive a minimum dose of 155 U Botulinum Toxin Type A Purified Neurotoxin Complex administered at 31 fixed-site, fixed-dose injections across seven (7) specific head/neck muscle areas at Visits 2-5.&#xD;
Placebo: Subjects randomized to the onabotulinumtoxinA + placebo group will receive:&#xD;
Week 1: placebo 25 mg qhs Week 2: placebo 25 mg bid Week 3: placebo 25 mg q am + placebo 50 mg qhs Week 4: placebo 50 mg bid Only one dosage adjustment (increase or decrease), based on efficacy or tolerability, may be made at the investigator's discretion. Subjects must maintain a dose of at least 50 mg/day to remain in the Treatment Period.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Non-Serious Adverse Events Between Groups</title>
          <population>All consenting participants.</population>
          <units>Adverse Events</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.60" spread="8.93"/>
                    <measurement group_id="O2" value="4.60" spread="3.17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Subject's Migraine Specific Quality of Life Questionnaire (MSQ) Scores at Baseline, 3, 6, 9 and 12 Months to Measure Subject's Quality of Life</title>
        <description>The Migraine-Specific Quality of Life Questionnaire (MSQ) is a scale that measures the impact of migraine across three aspects: role function-restrictive (RR), role function-preventive (RP), and emotional function (EF). Possible scores on each sub-scale range from a 0 to 100 scale such that higher scores indicate better quality of life.</description>
        <time_frame>Baseline, Months: 3, 6, 9 and 12</time_frame>
        <population>Number of participants vary at each visit based on the number of those still enrolled in the study at the time of the visit.</population>
        <group_list>
          <group group_id="O1">
            <title>OnabotulinumtoxinA + Topiramate</title>
            <description>Subject will receive 155 U onabotulinumtoxinA injections at 31 sites every 3 months for 12 months and treat daily with topiramate. During the first month of the treatment period, subjects will titrate as follows:&#xD;
Week 1: topiramate 25 mg qhs Week 2: topiramate 25 mg bid Week 3: topiramate 25 mg q am + topiramate 50 mg qhs Week 4: topiramate 50 mg bid Only one dosage adjustment (increase or decrease), based on efficacy or tolerability, may be made at the investigator's discretion. Subjects must maintain a dose of at least 50 mg/day to remain in the Treatment Period.&#xD;
onabotulinumtoxinA: All subjects will receive a minimum dose of 155 U Botulinum Toxin Type A Purified Neurotoxin Complex administered at 31 fixed-site, fixed-dose injections across seven (7) specific head/neck muscle areas at Visits 2-5.&#xD;
Topiramate: Subjects randomized to the onabotulinumtoxinA + topiramate group will receive:&#xD;
Week 1: topiramate 25 mg qhs Week 2: topiramate 25 mg bid Week 3: topiramate</description>
          </group>
          <group group_id="O2">
            <title>OnabotulinumtoxinA + Placebo</title>
            <description>Subject will receive 155 U onabotulinumtoxinA injections at 31 sites every 3 months for 12 months and treat daily with placebo. During the first month of the treatment period, subjects will titrate as follows:&#xD;
Week 1: 1 tab qhs Week 2: 1 tab bid Week 3: 1 tab q am + 2 tabs qhs Week 4: 2 tabs bid&#xD;
onabotulinumtoxinA: All subjects will receive a minimum dose of 155 U Botulinum Toxin Type A Purified Neurotoxin Complex administered at 31 fixed-site, fixed-dose injections across seven (7) specific head/neck muscle areas at Visits 2-5.&#xD;
Placebo: Subjects randomized to the onabotulinumtoxinA + placebo group will receive:&#xD;
Week 1: placebo 25 mg qhs Week 2: placebo 25 mg bid Week 3: placebo 25 mg q am + placebo 50 mg qhs Week 4: placebo 50 mg bid Only one dosage adjustment (increase or decrease), based on efficacy or tolerability, may be made at the investigator's discretion. Subjects must maintain a dose of at least 50 mg/day to remain in the Treatment Period.</description>
          </group>
        </group_list>
        <measure>
          <title>Subject's Migraine Specific Quality of Life Questionnaire (MSQ) Scores at Baseline, 3, 6, 9 and 12 Months to Measure Subject's Quality of Life</title>
          <description>The Migraine-Specific Quality of Life Questionnaire (MSQ) is a scale that measures the impact of migraine across three aspects: role function-restrictive (RR), role function-preventive (RP), and emotional function (EF). Possible scores on each sub-scale range from a 0 to 100 scale such that higher scores indicate better quality of life.</description>
          <population>Number of participants vary at each visit based on the number of those still enrolled in the study at the time of the visit.</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="10"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Role Function-Restrictive - Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                    <count group_id="O2" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="32.14" spread="16.62"/>
                    <measurement group_id="O2" value="29.71" spread="14.77"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Role Function-Restrictive - Month 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="9"/>
                    <count group_id="O2" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="56.51" spread="25.18"/>
                    <measurement group_id="O2" value="56.29" spread="25.16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Role Function-Restrictive - Month 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="9"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="77.14" spread="10.22"/>
                    <measurement group_id="O2" value="59.37" spread="21.94"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Role Function-Restrictive - Month 9</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="79.52" spread="13.21"/>
                    <measurement group_id="O2" value="60.41" spread="25.52"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Role Function-Restrictive - Month 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="81.90" spread="12.21"/>
                    <measurement group_id="O2" value="72.38" spread="24.36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Role Function-Preventive - Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                    <count group_id="O2" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="56.50" spread="22.61"/>
                    <measurement group_id="O2" value="46.50" spread="24.39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Role Function-Preventive - Month 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="9"/>
                    <count group_id="O2" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="72.78" spread="26.82"/>
                    <measurement group_id="O2" value="65.00" spread="28.28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Role Function-Preventive - Month 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="9"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="90.00" spread="8.37"/>
                    <measurement group_id="O2" value="72.22" spread="26.94"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Role Function-Preventive - Month 9</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="88.33" spread="8.16"/>
                    <measurement group_id="O2" value="72.86" spread="26.28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Role Function-Preventive - Month 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="96.67" spread="2.58"/>
                    <measurement group_id="O2" value="80.83" spread="24.98"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Emotional Function - Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                    <count group_id="O2" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="39.33" spread="30.70"/>
                    <measurement group_id="O2" value="22.67" spread="22.04"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Emotional Function - Month 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="9"/>
                    <count group_id="O2" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="57.78" spread="36.67"/>
                    <measurement group_id="O2" value="56.67" spread="33.15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Emotional Function - Month 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="9"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="88.89" spread="6.89"/>
                    <measurement group_id="O2" value="56.30" spread="32.51"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Emotional Function - Month 9</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="92.22" spread="16.01"/>
                    <measurement group_id="O2" value="70.48" spread="29.02"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Emotional Function - Month 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="95.56" spread="8.07"/>
                    <measurement group_id="O2" value="78.89" spread="28.10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>OnabotulinumtoxinA + Topiramate</title>
          <description>Subject will receive 155 U onabotulinumtoxinA injections at 31 sites every 3 months for 12 months and treat daily with topiramate. During the first month of the treatment period, subjects will titrate as follows:&#xD;
Week 1: topiramate 25 mg qhs Week 2: topiramate 25 mg bid Week 3: topiramate 25 mg q am + topiramate 50 mg qhs Week 4: topiramate 50 mg bid Only one dosage adjustment (increase or decrease), based on efficacy or tolerability, may be made at the investigator's discretion. Subjects must maintain a dose of at least 50 mg/day to remain in the Treatment Period.&#xD;
onabotulinumtoxinA: All subjects will receive a minimum dose of 155 U Botulinum Toxin Type A Purified Neurotoxin Complex administered at 31 fixed-site, fixed-dose injections across seven (7) specific head/neck muscle areas at Visits 2-5.</description>
        </group>
        <group group_id="E2">
          <title>OnabotulinumtoxinA + Placebo</title>
          <description>Subject will receive 155 U onabotulinumtoxinA injections at 31 sites every 3 months for 12 months and treat daily with placebo. During the first month of the treatment period, subjects will titrate as follows:&#xD;
Week 1: 1 tab qhs Week 2: 1 tab bid Week 3: 1 tab q am + 2 tabs qhs Week 4: 2 tabs bid&#xD;
onabotulinumtoxinA: All subjects will receive a minimum dose of 155 U Botulinum Toxin Type A Purified Neurotoxin Complex administered at 31 fixed-site, fixed-dose injections across seven (7) specific head/neck muscle areas at Visits 2-5.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Cardiac Arrest</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Rectal Proplapse</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Cholecystitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Septic Shock</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Renal Failure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="10"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Vertigo</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E2" events="5" subjects_affected="4" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased Cognition</sub_title>
                <counts group_id="E1" events="6" subjects_affected="5" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Sinus Infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Roger Cady</name_or_title>
      <organization>Clinvest/A Division of Banyan Group Inc.</organization>
      <phone>417-883-7889</phone>
      <email>rcady@banyangroupinc.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/NCT01700387
org study id: 12-001AL
secondary id: 71403
nct id: NCT01700387
lead sponsor: 
collaborator: 
has dmc: Yes
The purpose of this study is to evaluate sustained tolerability, quality of life, and change
      in cognitive efficiency following treatment with OnabotulinumtoxinA and daily topiramate vs.
      OnabotulinumtoxinA and daily placebo (Group A vs. Group B).
Numerous migraine preventive medications are well known to be associated with cognitive
      impairment and disruption of mood.

      Clinvest would propose a pilot study of chronic migraine patients randomized 1:1 to
      onabotulinumtoxinA and daily topiramate or onabotulinumtoxinA and placebo. This pilot study
      will examine the degree to which subjects are able to tolerate and are satisfied with a
      migraine preventive medication in addition to onabotulinumtoxinA over an extended period of
      time and the effect of the subjects' quality of life compared with onabotulinumtoxinA as a
      single therapy. It will also assess short and long term effects of these two treatments on
      cognition. Cognitive performance will be measured by the Mental Efficiency Workload Test
      (MEWT), a repeated measures handheld neuropsychological test battery that measures mental
      efficiency via 4 sub-tests (Simple Reaction Time, Running Memory, Continuous Performance
      Task, Matching to Sample, and Mathematical Processing) to demonstrate short and long term
      changes in mental status compared to their baseline. The Controlled Oral Word Association
      Test (COWAT) will be used to test verbal fluency and screen for anomic aphasia, a known side
      effect of several migraine prophylactic medications including topiramate.

      Visit 1 - Screening / Baseline Following Informed Consent a medical, headache, and medication
      history will be collected and a physical and neurological exam performed on all subjects. A
      urine pregnancy test will be collected from any subject of child-bearing potential. Vital
      signs and ECG (at the discretion of the investigator) will be completed. The Mental
      Efficiency Workload Test (MEWT) will be administered 3 times to establish a cognitive
      efficiency baseline. The COWAT will be completed. Subjects will be instructed regarding
      completion of the online 1-month Baseline Period Migraine Diary and be instructed to treat
      headaches during the 1-month Baseline Period with their usual acute migraine medication in
      their usual manner.

      Visit 2 - Randomization / Injection Following the 1-month Baseline Period, any change in
      medical or medication history since the previous visit will be collected and a pregnancy test
      collected if appropriate. Vital signs will be recorded. Subjects continuing to meet
      eligibility criteria will be instructed to complete the online Treatment Period Migraine
      Diary daily. The MEWT, HIT-6, Migraine Specific Questionnaire (MSQ) and COWAT will be
      completed. The coordinator will assess compliance with online headache diary and any
      deviation outside of 100% compliance should be documented at the site. If in the
      investigator's opinion, the subject maintained a high level of compliance with the online
      headache diary, subjects will then be randomized into the study.

      Eligible subjects will be randomized 1:1 in a blinded fashion to receive onabotulinumtoxinA
      at 31 fixed-site, fixed-dose injections across seven (7) specific head/neck muscle areas and
      daily topiramate (Group A) or onabotulinumtoxinA at 31 fixed-site, fixed-dose injections
      across seven (7) specific head/neck muscle areas and placebo to match topiramate (Group B).

      Daily study medication (topiramate or placebo) will be dispensed for the following 3 months.

      The Group A topiramate titration schedule will be as follows:

      Week 1: topiramate 25 mg qhs (every night at bedtime) Week 2: topiramate 25 mg bid (twice a
      day) Week 3: topiramate 25 mg q am (everyday before noon) + topiramate 50 mg qhs Week 4:
      topiramate 50mg bid

      Only one dosage adjustment (increase or decrease), based on efficacy or tolerability, may be
      made at the investigator's discretion. Subjects must maintain a dose of at least 50 mg/day to
      remain in the Treatment Period.

      The Group B placebo schedule will be as following:

      Week 1: 1 tab qhs Week 2: 1 tab bid Week 3: 1 tab q am + 2 tabs qhs Week 4: 2 tabs bid

      Subjects will be instructed to complete the online daily Treatment Period Migraine Diary
      during the next 3-month period.

      Following Visit 2, subjects will be phoned monthly and any adverse events collected. Subjects
      will also be sent weekly reminders for 8 weeks following Visit 2 via email to take study
      medication, complete online diary and contact their coordinator for any questions or concerns
      they may have. During the titration period, any subject in Group A experiencing an adverse
      event thought to be related to study medication dosage will return to the clinic at an
      Unscheduled Visit for dosage adjustment.

      Visit 3

      Three months following Visit 2, subjects will return and complete the MEWT, HIT-6, MSQ,
      COWAT, and Subject's Global Impression of Change (SGIC). The Investigator will complete a
      Physician's Global Impression of Change (PGIC). Any change in medical or medication history
      since the previous visit will be collected and a pregnancy test collected if appropriate.
      Vital signs will be recorded. The coordinator will assess compliance with online headache
      diary and any deviation outside of 100% compliance should be documented at the site. If in
      the investigator's opinion, the subject maintained a high level of compliance with the online
      headache diary, subjects will be allowed to continue in the study.

      All subjects will be administered a dose of 155 U onabotulinumtoxinA at 31 fixed-site,
      fixed-dose injections across seven (7) specific head/neck muscle areas.

      Any unused study medication and used packaging will be collected, drug accountability will be
      performed, and daily study medication (topiramate or placebo) will be dispensed for the
      following 3 months.

      Subjects will be instructed to complete the online daily Treatment Period Migraine Diary
      during the next 3-month period.

      Following Visit 3, subjects will be phoned monthly and any adverse events collected.

      Visit 4

      Three months following Visit 3, subjects will return and complete the MEWT, HIT-6, MSQ,
      COWAT, and Subject's Global Impression of Change (SGIC). The Investigator will complete a
      Physician's Global Impression of Change (PGIC). Any change in medical or medication history
      since the previous visit will be collected and a pregnancy test collected if appropriate.
      Vital signs will be recorded. The coordinator will assess compliance with online headache
      diary and any deviation outside of 100% compliance should be documented at the site.

      All subjects will be administered a dose of 155 U onabotulinumtoxinA at 31 fixed-site,
      fixed-dose injections across seven (7) specific head/neck muscle areas.

      Any unused study medication and used packaging will be collected, drug accountability will be
      performed, and daily study medication (topiramate or placebo) will be dispensed for the
      following 3 months.

      Subjects will be instructed to complete the online daily Treatment Period Migraine Diary
      during the next 3-month period.

      Following Visit 4, subjects will be phoned monthly and any adverse events collected.

      Visit 5

      Three months following Visit 4, subjects will return and complete the MEWT, HIT-6, MSQ,
      COWAT, and Subject's Global Impression of Change (SGIC). The Investigator will complete a
      Physician's Global Impression of Change (PGIC). Any change in medical or medication history
      since the previous visit will be collected and a pregnancy test collected if appropriate.
      Vital signs will be recorded. The coordinator will assess compliance with online headache
      diary and any deviation outside of 100% compliance should be documented at the site.

      All subjects will be administered a dose of 155 U onabotulinumtoxinA at 31 fixed-site,
      fixed-dose injections across seven (7) specific head/neck muscle areas.

      Any unused study medication and used packaging will be collected, drug accountability will be
      performed, and daily study medication (topiramate or placebo) will be dispensed for the
      following 3 months.

      Subjects will be instructed to complete the online daily Treatment Period Migraine Diary
      during the next 3-month period.

      Following Visit 5, subjects will be phoned monthly and any adverse events collected.

      Visit 6

      Three months following Visit 5, subjects will return and complete the MEWT, HIT-6, MSQ,
      COWAT, and Subject's Global Impression of Change. The Investigator will complete a
      Physician's Global Impression of Change. Any change in medical or medication history since
      the previous visit will be collected and a pregnancy test collected if appropriate. Vital
      signs will be recorded. The coordinator will assess compliance with online headache diary and
      any deviation outside of 100% compliance should be documented at the site.

      Any unused study medication and used packaging will be collected and drug accountability will
      be performed.

      Subjects will exit the study at Visit 6.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Subject Attrition Post Randomization
time frame: Collected on Visit 2 (Day 29) through Visit 6 (Day 365)
description: Count of subject attrition following randomization and reason for attrition (Consent withdrawn, Withdrawn due to adverse event, Lost to follow up)
measure: Subject Global Impression of Change (SGIC)
time frame: Collected on Visit 3 (Day 113), Visit 4 (Day 197), Visit 5 (281), and Visit 6 (Day 365)
description: Score on Subject Global Impression of Change at Visits 3-6 (Day 113 and 365). Likert scale ranging from 1-7, where 1 = extremely worse and 7 = extremely better.
measure: Physician Global Impression of Change (PGIC)
time frame: Collected on Visit 3 (Day 113), Visit 4 (Day 197), Visit 5 (281), and Visit 6 (Day 365)
description: Score on Physician Global Impression of Change at Visits 3-6 (Day 113 and 365). Likert scale ranging from 1-7, where 1 = extremely worse and 7 = extremely better.
measure: Subject's Controlled Oral Word Association Test (COWAT) Score Percent Change Compared From Baseline to Visits 3-6
time frame: Baseline, Visit 3 (Day 113) through Visit 6 (Day 365)
description: The Controlled Oral Word Association Test (COWAT) is a measure of verbal fluency. Raw COWAT scores have a lower bound of 0 with no upper bound. Higher scores indicate better verbal fluency. COWAT score percent change from baseline will be reported. Positive change scores represent better verbal fluency compared to baseline.
measure: Number of Headache Days
time frame: Baseline and Months 1-12
description: Number of Headache Days reported in 30-day Baseline Period and Treatment Period Months 1-12
measure: Headache Impact Test (HIT-6) Scores at Visits 2-6 to Measure Effect of Headache in Subject's Life
time frame: Collected on Visit 2 (Day 29), 3 (Day 113), Visit 4 (Day 197), Visit 5 (281), and Visit 6 (Day 365)
description: The Headache Impact Test (HIT-6) is a tool used to measure the impact headaches have on an individual's ability to function on the job, at school, at home and in social situations. The HIT-6 score range is from 36 to 78 with higher scores indicating greater impact (worse outcome).
measure: MEWT Simple Reaction Time Sub-test Score Percent Change Compared From Baseline to Visits 3-6
time frame: Baseline, Visit 3 (Day 113), Visit 4 (Day 197), Visit 5 (281), and Visit 6 (Day 365)
description: The Mental Efficiency Workload Test (MEWT) is a cognitive functioning scale with four sub-scales (Simple Reaction Time, Running Memory Continuous Performance Task, Matching to Sample, and Mathematical Processing). Each sub-scale has a minimum and maximum values of 1 to 10, 1 indicates the poorest level and 10 indicates the best level of cognitive functioning. MEWT sub-scale score percent change from baseline will be reported. Positive change scores represent better cognitive functioning compared to baseline.
measure: MEWT Running Memory Continuous Performance Task Sub-test Score Percent Change Compared From Baseline to Visits 3-6
time frame: Baseline, Visit 3 (Day 113), Visit 4 (Day 197), Visit 5 (281), and Visit 6 (Day 365)
description: The Mental Efficiency Workload Test (MEWT) is a cognitive functioning scale with four sub-scales (Simple Reaction Time, Running Memory Continuous Performance Task, Matching to Sample, and Mathematical Processing). Each sub-scale has a minimum and maximum values of 1 to 10, 1 indicates the poorest level and 10 indicates the best level of cognitive functioning. MEWT sub-scale score percent change from baseline will be reported. Positive change scores represent better cognitive functioning compared to baseline.
measure: MEWT Matching to Sample Sub-test Score Percent Change Compared From Baseline to Visits 3-6
time frame: Baseline, Visit 3 (Day 113), Visit 4 (Day 197), Visit 5 (281), and Visit 6 (Day 365)
description: The Mental Efficiency Workload Test (MEWT) is a cognitive functioning scale with four sub-scales (Simple Reaction Time, Running Memory Continuous Performance Task, Matching to Sample, and Mathematical Processing). Each sub-scale has a minimum and maximum values of 1 to 10, 1 indicates the poorest level and 10 indicates the best level of cognitive functioning. MEWT sub-scale score percent change from baseline will be reported. Positive change scores represent better cognitive functioning compared to baseline.
measure: MEWT Mathematical Processing Sub-test Score Percent Change Compared From Baseline to Visits 3-6
time frame: Baseline, Visit 3 (Day 113), Visit 4 (Day 197), Visit 5 (281), and Visit 6 (Day 365)
description: The Mental Efficiency Workload Test (MEWT) is a cognitive functioning scale with four sub-scales (Simple Reaction Time, Running Memory Continuous Performance Task, Matching to Sample, and Mathematical Processing). Each sub-scale has a minimum and maximum values of 1 to 10, 1 indicates the poorest level and 10 indicates the best level of cognitive functioning. MEWT sub-scale score percent change from baseline will be reported. Positive change scores represent better cognitive functioning compared to baseline.
measure: Subject Estimation of Compliance With Daily Study Drug
time frame: Collected on Visit 2 (Day 29), 3 (Day 113), Visit 4 (Day 197), and Visit 5 (281)
description: Subject estimation of compliance with daily study drug during the study period. Compliance ranges from 0% to 100% with higher percentages indicating greater compliance with study drug.
measure: Number of Non-Serious Adverse Events Between Groups
time frame: 13 Months (Visit 1 to Visit 6)
measure: Subject's Migraine Specific Quality of Life Questionnaire (MSQ) Scores at Baseline, 3, 6, 9 and 12 Months to Measure Subject's Quality of Life
time frame: Baseline, Months: 3, 6, 9 and 12
description: The Migraine-Specific Quality of Life Questionnaire (MSQ) is a scale that measures the impact of migraine across three aspects: role function-restrictive (RR), role function-preventive (RP), and emotional function (EF). Possible scores on each sub-scale range from a 0 to 100 scale such that higher scores indicate better quality of life.
arm group label: OnabotulinumtoxinA + Topiramate
arm group type: Experimental
description: Subject will receive 155 U onabotulinumtoxinA injections at 31 sites every 3 months for 12 months and treat daily with topiramate. During the first month of the treatment period, subjects will titrate as follows:
Week 1: topiramate 25 mg qhs Week 2: topiramate 25 mg bid Week 3: topiramate 25 mg q am + topiramate 50 mg qhs Week 4: topiramate 50 mg bid Only one dosage adjustment (increase or decrease), based on efficacy or tolerability, may be made at the investigator's discretion. Subjects must maintain a dose of at least 50 mg/day to remain in the Treatment Period.
arm group label: OnabotulinumtoxinA + Placebo
arm group type: Placebo Comparator
description: Subject will receive 155 U onabotulinumtoxinA injections at 31 sites every 3 months for 12 months and treat daily with placebo. During the first month of the treatment period, subjects will titrate as follows:
Week 1: 1 tab qhs Week 2: 1 tab bid Week 3: 1 tab q am + 2 tabs qhs Week 4: 2 tabs bid
intervention type: Drug
intervention name: onabotulinumtoxinA
description: All subjects will receive a minimum dose of 155 U Botulinum Toxin Type A Purified Neurotoxin Complex administered at 31 fixed-site, fixed-dose injections across seven (7) specific head/neck muscle areas at Visits 2-5.
arm group label: OnabotulinumtoxinA + Placebo
arm group label: OnabotulinumtoxinA + Topiramate
other name: Botox, Botulinum Toxin Type A Purified Neurotoxin Complex
intervention type: Drug
intervention name: Topiramate
description: Subjects randomized to the onabotulinumtoxinA + topiramate group will receive:
Week 1: topiramate 25 mg qhs Week 2: topiramate 25 mg bid Week 3: topiramate 25 mg q am + topiramate 50 mg qhs Week 4: topiramate 50 mg bid Only one dosage adjustment (increase or decrease), based on efficacy or tolerability, may be made at the investigator's discretion. Subjects must maintain a dose of at least 50 mg/day to remain in the Treatment Period.
arm group label: OnabotulinumtoxinA + Topiramate
other name: Topamax
intervention type: Drug
intervention name: Placebo
description: Subjects randomized to the onabotulinumtoxinA + placebo group will receive:
Week 1: placebo 25 mg qhs Week 2: placebo 25 mg bid Week 3: placebo 25 mg q am + placebo 50 mg qhs Week 4: placebo 50 mg bid Only one dosage adjustment (increase or decrease), based on efficacy or tolerability, may be made at the investigator's discretion. Subjects must maintain a dose of at least 50 mg/day to remain in the Treatment Period.
arm group label: OnabotulinumtoxinA + Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Roger K Cady, MD
role: Principal Investigator
affiliation: Clinvest
facility: 
country: United States
citation: Bootsma HP, Aldenkamp AP, Diepman L, Hulsman J, Lambrechts D, Leenen L, Majoie M, Schellekens A, de Krom M. The Effect of Antiepileptic Drugs on Cognition: Patient Perceived Cognitive Problems of Topiramate versus Levetiracetam in Clinical Practice. Epilepsia. 2006;47 Suppl 2:24-7. doi: 10.1111/j.1528-1167.2006.00683.x.
PMID: 17105455
citation: Kim SY, Lee HW, Jung DK, Suh CK, Park SP. Cognitive Effects of Low-dose Topiramate Compared with Oxcarbazepine in Epilepsy Patients. J Clin Neurol. 2006 Jun;2(2):126-33. doi: 10.3988/jcn.2006.2.2.126. Epub 2006 Jun 20.
PMID: 20396496
citation: Meador KJ, Loring DW, Vahle VJ, Ray PG, Werz MA, Fessler AJ, Ogrocki P, Schoenberg MR, Miller JM, Kustra RP. Cognitive and behavioral effects of lamotrigine and topiramate in healthy volunteers. Neurology. 2005 Jun 28;64(12):2108-14. doi: 10.1212/01.WNL.0000165994.46777.BE.
PMID: 15985582
responsible party type: Sponsor
mesh term: Migraine Disorders
mesh term: Topiramate
mesh term: Botulinum Toxins
mesh term: Botulinum Toxins, Type A
mesh term: abobotulinumtoxinA
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 