<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/NCT03828539</url>
  </required_header>
  <id_info>
    <org_study_id>CAMG334ADE01</org_study_id>
    <secondary_id>2018-000943-15</secondary_id>
    <nct_id>NCT03828539</nct_id>
  </id_info>
  <brief_title>Head-to-head Study of Erenumab Against Topiramate in Patients With Episodic and Chronic Migraine</brief_title>
  <acronym>HER-MES</acronym>
  <official_title>Head-to-head Study of Erenumab Against topiRamate-a Double-blind, Double Dummy Migraine Study to Assess Tolerability and Efficacy in a patiEnt -Centered Setting</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Novartis Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Novartis</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study used a single-cohort, 2-treatment arm, parallel-group randomized, double-blind,&#xD;
      double-dummy design in adult patients with episodic migraine and chronic migraine, who had to&#xD;
      be either naïve or not suitable for or could have failed up to three prophylactic treatments&#xD;
      out of: propranolol/metoprolol, amitriptyline, flunarizine. Patients were stratified into&#xD;
      groups according to their number of migraine days during the baseline period.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      All patients completing the Baseline period and fulfilling baseline eligibility criteria were&#xD;
      invited to participate to the Double-blind, double-dummy Treatment Epoch (DBTE, 24 weeks) .&#xD;
&#xD;
      Eligible patients were randomized to one of two treatment arms. DBTE started with a titration&#xD;
      phase for topiramate of a maximum of 6 weeks to determine the maximal tolerated dose and&#xD;
      aimed to reach the recommended treatment dose of 100 mg according to the German SmPC. After&#xD;
      the titration phase, maintenance phase started (18 weeks). Topiramate dose had to be&#xD;
      maintained until the end of the DBTE. Erenumab dose at beginning of the DBTE was determined&#xD;
      patient individually by the investigator based on the guidance provided in the SmPC and was&#xD;
      either 70 mg or 140 mg. Dose escalation from 70 mg to 140 mg in case of insufficient response&#xD;
      was considered at anytime during the DBTE.&#xD;
&#xD;
      Dose reduction of topiramate and erenumab was not allowed during DBTE (Week 0 to Week 24).&#xD;
      After Week 24 or if the patient discontinued study drug, a one week double-blind taper off&#xD;
      phase followed to ensure proper down titration for topiramate. At the end of the DBTE (24&#xD;
      weeks) the final assessment occurred to address the objectives.&#xD;
&#xD;
      A Follow-Up Visit 4 weeks after last study visit (or 8 weeks after last IMP injection for&#xD;
      discontinued patients) was required as part of routine safety monitoring. The primary&#xD;
      analysis was triggered when all patients had completed their respective last visit of the&#xD;
      DBTE.&#xD;
&#xD;
      The End of study occurred when the last patient completed last visit (LPLV).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 22, 2019</start_date>
  <completion_date type="Actual">July 29, 2020</completion_date>
  <primary_completion_date type="Actual">July 29, 2020</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>Prevention</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Proportion of Patients With Treatment Discontinuation Due to an Adverse Event (AE) During the Double-blind Treatment Epoch/Period (DBTE)</measure>
    <time_frame>24 Weeks</time_frame>
    <description>The primary objective was to demonstrate the tolerability of 70 mg and 140 mg erenumab compared to topiramate in the highest tolerated dose assessed by the rate of patients discontinuing treatment due to AE during the double-blind epoch of the study.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Patients With at Least 50% Reduction From Baseline in Monthly Migraine Days (MMD) Over the Last Three Months (Month 4, 5, and 6)</measure>
    <time_frame>Baseline, Last three months (month 4, 5, and 6)</time_frame>
    <description>The secondary objective of this study was to evaluate the effect of erenumab compared to topiramate on the proportion of patients with at least 50% reduction from baseline in MMDs. The Baseline period was defined as the period between Week -4 and the day prior to first dose. This was analyzed by logistic regression over the last 3 months (months 4, 5, and 6) of treatment. All the subjects' data collected regarding 50% response in MMD was used in the analysis regardless of whether subjects discontinue study treatment or not. Subjects with missing response information on this endpoint were imputed as non-response (non-responder imputation).</description>
  </secondary_outcome>
  <other_outcome>
    <measure>EXPLORATORY ENDPOINT: Proportion of Patients Achieving at Least a 5 Points Reduction in the Headache Impact Test (HIT-6) From Baseline to Week 24</measure>
    <time_frame>Baseline, Week 24</time_frame>
    <description>The HIT-6 is a widely used patient-reported outcome measure that assesses the negative effects of headaches on normal activity. Six items assess the frequency of pain severity, headaches limiting daily activity (household, work, school, and social), wanting to lie down when headache is experienced, feeling too tired to work or do daily activities because of headache, feeling &quot;fed up&quot; or irritated because of headache, and headaches limiting ability to concentrate or work on daily activities. Each of the 6 questions is responded to using 1 of 5 response categories: &quot;never,&quot; &quot;rarely,&quot; &quot;sometimes,&quot; &quot;very often,&quot; or &quot;always.&quot; For each HIT-6 item, 6, 8, 10, 11, or 13 points, respectively, are assigned to the response provided. These points are summed to produce a total HIT-6 score that ranges from 36 to 78. HIT-6 scores are categorized into 4 grades: little or no impact (49 or less), some impact (50 - 55), substantial impact (56 - 59), and severe impact (60 - 78) due to headache.</description>
  </other_outcome>
  <other_outcome>
    <measure>EXPLORATORY ENDPOINT: Proportion of Patients Achieving at Least a 5 Points Increase in the Medical Outcome Short Form Health Survey Version 2 (SF-36) From Baseline to Week 24</measure>
    <time_frame>Baseline, Week 24</time_frame>
    <description>The SF-36 is a widely used and extensively studied instrument to measure health-related quality of life (HRQoL) among healthy subjects and patients with acute and chronic conditions. It consists of eight subscales that can be scored individually: Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional, and Mental Health. Two overall summary scores, the Physical Component Summary (PCS) and the Mental Component Summary (MCS) also can be computed. The SF-36 has proven useful in monitoring general and specific populations, comparing the relative burden of different disease, differentiating the health benefits produced by different treatments, and in screening individual patients. The purpose of the SF-36 in this study was to assess the HRQoL of patients. Given the nature of this disease and the 4-weekly assessment, the SF-36 version 2, with a 4-week recall period, was used in this study.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">777</enrollment>
  <condition>Migraine</condition>
  <arm_group>
    <arm_group_label>Erenumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>70 mg and 140 mg Erenumab</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Topiramate</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Topiramate in the highest tolerated dose (50 - 100 mg/day)</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Erenumab</intervention_name>
    <description>70mg/1mL (70 mg) or 2x70mg/1mL (140 mg) in pre-filled syringe, administered every 4 weeks</description>
    <arm_group_label>Erenumab</arm_group_label>
    <other_name>AMG334</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Topiramate</intervention_name>
    <description>Film-coated tablet taken orally:&#xD;
25 mg administered once daily (first week of titration phase). After the first week, titration was done according to the summary of product characteristics (SmPC) in 25 mg increments each week and aimed to reach the recommended daily treatment dose of 100 mg (50/75/100 mg). 50/75/100 mg were administered twice daily during titration phase and maintenance phase.</description>
    <arm_group_label>Topiramate</arm_group_label>
    <other_name>Topamax</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Erenumab matching placebo</intervention_name>
    <description>Erenumab matching placebo pre-filled syringue administered every 4 weeks</description>
    <arm_group_label>Erenumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Topiramate matching placebo</intervention_name>
    <description>Topiramate matching placebo administered daily</description>
    <arm_group_label>Topiramate</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria:&#xD;
&#xD;
          1. Documented history of migraine in the 12 months prior to screen&#xD;
&#xD;
          2. at least 4 days per month of migraine symptoms&#xD;
&#xD;
          3. &gt;=80% diary compliance during the Baseline period&#xD;
&#xD;
          4. Patients must be either naïve or not suitable or have failed previous migraine&#xD;
             prophylactic treatments&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
          1. Older than 50 years of age at migraine onset&#xD;
&#xD;
          2. Pregnant or nursing&#xD;
&#xD;
          3. History of cluster or hemiplegic headache&#xD;
&#xD;
          4. History or evidence of major psychiatric disorder&#xD;
&#xD;
          5. Score of 19 or higher on Beck Depression Inventory (BDI)&#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>Novartis Pharmaceuticals</last_name>
    <role>Study Director</role>
    <affiliation>Novartis Pharmaceuticals</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Stuttgart</city>
        <state>Baden Wuertemberg</state>
        <zip>70178</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Hannover</city>
        <state>Niedersachsen</state>
        <zip>30159</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Aachen</city>
        <state>Nordrhein-Westfalen</state>
        <zip>52062</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Alzenau</city>
        <zip>63755</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Bad Homburg</city>
        <zip>61348</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Bad Honnef</city>
        <zip>53604</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Bad Saarow</city>
        <zip>15526</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Bayreuth</city>
        <zip>95445</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Bergen</city>
        <zip>18528</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Berlin</city>
        <zip>10713</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Berlin</city>
        <zip>120999</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Berlin</city>
        <zip>12101</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Berlin</city>
        <zip>12163</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Berlin</city>
        <zip>12627</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Berlin</city>
        <zip>13156</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Berlin</city>
        <zip>13353</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Berlin</city>
        <zip>14169</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Bielefeld</city>
        <zip>D 33647</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Boblingen</city>
        <zip>71032</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Bochum</city>
        <zip>44791</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Bonn</city>
        <zip>53111</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Bonn</city>
        <zip>53177</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Celle</city>
        <zip>29223</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Chemnitz</city>
        <zip>09117</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Dillingen</city>
        <zip>66763</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Erbach</city>
        <zip>64711</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Essen</city>
        <zip>45133</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Essen</city>
        <zip>45147</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Frankfurt</city>
        <zip>60313</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Freiburg</city>
        <zip>79098</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Gelsenkirchen</city>
        <zip>45879</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Greifswald</city>
        <zip>17475</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Haar</city>
        <zip>85540</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Halle</city>
        <zip>06120</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Hamburg</city>
        <zip>20253</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Heidelberg</city>
        <zip>69120</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Heidenheim</city>
        <zip>89518</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Hoppegarten</city>
        <zip>15366</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Ibbenbueren</city>
        <zip>49477</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Jena</city>
        <zip>07740</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Juelich</city>
        <zip>52428</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Kassel</city>
        <zip>34121</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Kassel</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Kiel</city>
        <zip>24149</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Koln</city>
        <zip>50935</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Königstein im Taunus</city>
        <zip>61462</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Leipzig</city>
        <zip>04103</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Leipzig</city>
        <zip>04107</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Luenen</city>
        <zip>44534</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Mannheim</city>
        <zip>66163</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Marburg Wehrda</city>
        <zip>35041</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Mittweida</city>
        <zip>09648</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Muenchen</city>
        <zip>81377</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Muenchen</city>
        <zip>81675</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Muenster</city>
        <zip>48149</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Neu-Ulm</city>
        <zip>89231</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Neuburg an der Donau</city>
        <zip>86633</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Osnabrück</city>
        <zip>49074</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Pforzheim</city>
        <zip>75172</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Quakenbrueck</city>
        <zip>49610</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Regensburg</city>
        <zip>93059</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Rostock</city>
        <zip>18057</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Ruelzheim</city>
        <zip>76761</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Schwerin</city>
        <zip>19053</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Schwerin</city>
        <zip>19055</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Seesen</city>
        <zip>38723</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Siegen</city>
        <zip>57076</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Sindelfingen</city>
        <zip>71065</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Stadtroda</city>
        <zip>07646</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Stuttgart</city>
        <zip>70174</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Stuttgart</city>
        <zip>70178</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Stuttgart</city>
        <zip>70182</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Trier</city>
        <zip>54292</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Tübingen</city>
        <zip>72076</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Ulm</city>
        <zip>89073</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Unterhaching</city>
        <zip>82008</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Westerstede/Oldenburg</city>
        <zip>26655</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Wiesbaden</city>
        <zip>65191</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Wuerzburg</city>
        <zip>97080</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <link>
    <url>https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=941</url>
    <description>A Plain Language Trial Summary is available on novartisclinicaltrials.com</description>
  </link>
  <verification_date>October 2021</verification_date>
  <study_first_submitted>February 1, 2019</study_first_submitted>
  <study_first_submitted_qc>February 1, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 4, 2019</study_first_posted>
  <results_first_submitted>July 16, 2021</results_first_submitted>
  <results_first_submitted_qc>July 16, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">August 9, 2021</results_first_posted>
  <last_update_submitted>October 7, 2021</last_update_submitted>
  <last_update_submitted_qc>October 7, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">October 11, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Migraine</keyword>
  <keyword>Episodic migraine</keyword>
  <keyword>Chronic migraine</keyword>
  <keyword>Headache</keyword>
  <keyword>erenumab</keyword>
  <keyword>topiramate</keyword>
  <keyword>CAMG 334</keyword>
  <keyword>Calcitonin Gene-related Peptide</keyword>
  <keyword>CGRP</keyword>
  <keyword>CGRP receptor agonist</keyword>
  <keyword>monoclonal antibody</keyword>
  <keyword>treatment failure</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>Erenumab</mesh_term>
    <mesh_term>Antibodies, Monoclonal</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.&#xD;
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com</ipd_description>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>June 6, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/39/NCT03828539/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>October 1, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/39/NCT03828539/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>82 centers in Germany enrolled patients.</recruitment_details>
      <pre_assignment_details>A total of 777 patients were randomized to receive either erenumab (389 patients) or topiramate (388 patients).</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Erenumab</title>
          <description>70 mg and 140 mg Erenumab</description>
        </group>
        <group group_id="P2">
          <title>Topiramate</title>
          <description>Topiramate in the highest tolerated dose (50 - 100 mg/day)</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="389"/>
                <participants group_id="P2" count="388"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Full Analysis Set (FAS)</title>
              <participants_list>
                <participants group_id="P1" count="388"/>
                <participants group_id="P2" count="388"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Safety Analysis Set (SAF)</title>
              <participants_list>
                <participants group_id="P1" count="388"/>
                <participants group_id="P2" count="388"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="373"/>
                <participants group_id="P2" count="366"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
                <participants group_id="P2" count="22"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="12"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Patient's/guardian's decision</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal of informed consent</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>New therapy for study indication</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Demographic variables and other baseline characteristics were summarized for each randomized treatment group and for all patients (total) using the Full Analysis set (FAS)</population>
      <group_list>
        <group group_id="B1">
          <title>Erenumab</title>
          <description>70 mg and 140 mg Erenumab</description>
        </group>
        <group group_id="B2">
          <title>Topiramate</title>
          <description>Topiramate in the highest tolerated dose (50 - 100 mg/day)</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="388"/>
            <count group_id="B2" value="388"/>
            <count group_id="B3" value="776"/>
          </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="40.8" spread="12.4"/>
                    <measurement group_id="B2" value="40.7" spread="12.4"/>
                    <measurement group_id="B3" value="40.7" spread="12.4"/>
                  </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="331"/>
                    <measurement group_id="B2" value="335"/>
                    <measurement group_id="B3" value="666"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="57"/>
                    <measurement group_id="B2" value="53"/>
                    <measurement group_id="B3" value="110"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Caucasian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="383"/>
                    <measurement group_id="B2" value="387"/>
                    <measurement group_id="B3" value="770"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Asian</title>
              <category_list>
                <category>
                  <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>
              <title>Unknown</title>
              <category_list>
                <category>
                  <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>
              <title>Other</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Baseline Monthly Migraine Days (MMDs) categories</title>
          <description>Monthly migraine days at baseline are the number of migraine days in the baseline period that are normalized in a 28-day interval. Monthly migraine days after baseline are the number of migraine days between each monthly IMP dose that are normalized in a 28-day interval. Days without eDiary data in each normalized monthly interval were prorated.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt; 4 days</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>4 to 7 days</title>
                  <measurement_list>
                    <measurement group_id="B1" value="94"/>
                    <measurement group_id="B2" value="92"/>
                    <measurement group_id="B3" value="186"/>
                  </measurement_list>
                </category>
                <category>
                  <title>8 to 14 days</title>
                  <measurement_list>
                    <measurement group_id="B1" value="248"/>
                    <measurement group_id="B2" value="254"/>
                    <measurement group_id="B3" value="502"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;= 15 days</title>
                  <measurement_list>
                    <measurement group_id="B1" value="43"/>
                    <measurement group_id="B2" value="42"/>
                    <measurement group_id="B3" value="85"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Missing</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_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Proportion of Patients With Treatment Discontinuation Due to an Adverse Event (AE) During the Double-blind Treatment Epoch/Period (DBTE)</title>
        <description>The primary objective was to demonstrate the tolerability of 70 mg and 140 mg erenumab compared to topiramate in the highest tolerated dose assessed by the rate of patients discontinuing treatment due to AE during the double-blind epoch of the study.</description>
        <time_frame>24 Weeks</time_frame>
        <population>Full Analysis Set (FAS)</population>
        <group_list>
          <group group_id="O1">
            <title>Erenumab</title>
            <description>70 mg and 140 mg Erenumab</description>
          </group>
          <group group_id="O2">
            <title>Topiramate</title>
            <description>Topiramate in the highest tolerated dose (50 - 100 mg/day)</description>
          </group>
        </group_list>
        <measure>
          <title>Proportion of Patients With Treatment Discontinuation Due to an Adverse Event (AE) During the Double-blind Treatment Epoch/Period (DBTE)</title>
          <description>The primary objective was to demonstrate the tolerability of 70 mg and 140 mg erenumab compared to topiramate in the highest tolerated dose assessed by the rate of patients discontinuing treatment due to AE during the double-blind epoch of the study.</description>
          <population>Full Analysis Set (FAS)</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="388"/>
                <count group_id="O2" value="388"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="41"/>
                    <measurement group_id="O2" value="151"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>&lt;.001</p_value>
            <method>Regression, Logistic</method>
            <method_desc>Odds ratio is obtained from a logistic regression model that includes treatment group and stratification factor (MMD at baseline)</method_desc>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>0.19</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.13</ci_lower_limit>
            <ci_upper_limit>0.27</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Patients With at Least 50% Reduction From Baseline in Monthly Migraine Days (MMD) Over the Last Three Months (Month 4, 5, and 6)</title>
        <description>The secondary objective of this study was to evaluate the effect of erenumab compared to topiramate on the proportion of patients with at least 50% reduction from baseline in MMDs. The Baseline period was defined as the period between Week -4 and the day prior to first dose. This was analyzed by logistic regression over the last 3 months (months 4, 5, and 6) of treatment. All the subjects' data collected regarding 50% response in MMD was used in the analysis regardless of whether subjects discontinue study treatment or not. Subjects with missing response information on this endpoint were imputed as non-response (non-responder imputation).</description>
        <time_frame>Baseline, Last three months (month 4, 5, and 6)</time_frame>
        <population>Full Analysis Set (FAS)</population>
        <group_list>
          <group group_id="O1">
            <title>Erenumab</title>
            <description>70 mg and 140 mg Erenumab</description>
          </group>
          <group group_id="O2">
            <title>Topiramate</title>
            <description>Topiramate in the highest tolerated dose (50 - 100 mg/day)</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients With at Least 50% Reduction From Baseline in Monthly Migraine Days (MMD) Over the Last Three Months (Month 4, 5, and 6)</title>
          <description>The secondary objective of this study was to evaluate the effect of erenumab compared to topiramate on the proportion of patients with at least 50% reduction from baseline in MMDs. The Baseline period was defined as the period between Week -4 and the day prior to first dose. This was analyzed by logistic regression over the last 3 months (months 4, 5, and 6) of treatment. All the subjects' data collected regarding 50% response in MMD was used in the analysis regardless of whether subjects discontinue study treatment or not. Subjects with missing response information on this endpoint were imputed as non-response (non-responder imputation).</description>
          <population>Full Analysis Set (FAS)</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="388"/>
                <count group_id="O2" value="388"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="215"/>
                    <measurement group_id="O2" value="121"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>&lt;.001</p_value>
            <method>Regression, Logistic</method>
            <method_desc>Odds ratio is obtained from a logistic regression model that includes treatment group and stratification factor (MMD at baseline)</method_desc>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>2.76</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>2.06</ci_lower_limit>
            <ci_upper_limit>3.71</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>EXPLORATORY ENDPOINT: Proportion of Patients Achieving at Least a 5 Points Reduction in the Headache Impact Test (HIT-6) From Baseline to Week 24</title>
        <description>The HIT-6 is a widely used patient-reported outcome measure that assesses the negative effects of headaches on normal activity. Six items assess the frequency of pain severity, headaches limiting daily activity (household, work, school, and social), wanting to lie down when headache is experienced, feeling too tired to work or do daily activities because of headache, feeling &quot;fed up&quot; or irritated because of headache, and headaches limiting ability to concentrate or work on daily activities. Each of the 6 questions is responded to using 1 of 5 response categories: &quot;never,&quot; &quot;rarely,&quot; &quot;sometimes,&quot; &quot;very often,&quot; or &quot;always.&quot; For each HIT-6 item, 6, 8, 10, 11, or 13 points, respectively, are assigned to the response provided. These points are summed to produce a total HIT-6 score that ranges from 36 to 78. HIT-6 scores are categorized into 4 grades: little or no impact (49 or less), some impact (50 - 55), substantial impact (56 - 59), and severe impact (60 - 78) due to headache.</description>
        <time_frame>Baseline, Week 24</time_frame>
        <population>Full Analysis Set (FAS)</population>
        <group_list>
          <group group_id="O1">
            <title>Erenumab</title>
            <description>70 mg and 140 mg Erenumab</description>
          </group>
          <group group_id="O2">
            <title>Topiramate</title>
            <description>Topiramate in the highest tolerated dose (50 - 100 mg/day)</description>
          </group>
        </group_list>
        <measure>
          <title>EXPLORATORY ENDPOINT: Proportion of Patients Achieving at Least a 5 Points Reduction in the Headache Impact Test (HIT-6) From Baseline to Week 24</title>
          <description>The HIT-6 is a widely used patient-reported outcome measure that assesses the negative effects of headaches on normal activity. Six items assess the frequency of pain severity, headaches limiting daily activity (household, work, school, and social), wanting to lie down when headache is experienced, feeling too tired to work or do daily activities because of headache, feeling &quot;fed up&quot; or irritated because of headache, and headaches limiting ability to concentrate or work on daily activities. Each of the 6 questions is responded to using 1 of 5 response categories: &quot;never,&quot; &quot;rarely,&quot; &quot;sometimes,&quot; &quot;very often,&quot; or &quot;always.&quot; For each HIT-6 item, 6, 8, 10, 11, or 13 points, respectively, are assigned to the response provided. These points are summed to produce a total HIT-6 score that ranges from 36 to 78. HIT-6 scores are categorized into 4 grades: little or no impact (49 or less), some impact (50 - 55), substantial impact (56 - 59), and severe impact (60 - 78) due to headache.</description>
          <population>Full Analysis Set (FAS)</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="388"/>
                <count group_id="O2" value="388"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="280"/>
                    <measurement group_id="O2" value="209"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>&lt;.001</p_value>
            <method>Regression, Logistic</method>
            <method_desc>Odds ratio is obtained from a logistic regression model that includes treatment group and stratification factor (MMD at baseline)</method_desc>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>2.30</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.70</ci_lower_limit>
            <ci_upper_limit>3.12</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>EXPLORATORY ENDPOINT: Proportion of Patients Achieving at Least a 5 Points Increase in the Medical Outcome Short Form Health Survey Version 2 (SF-36) From Baseline to Week 24</title>
        <description>The SF-36 is a widely used and extensively studied instrument to measure health-related quality of life (HRQoL) among healthy subjects and patients with acute and chronic conditions. It consists of eight subscales that can be scored individually: Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional, and Mental Health. Two overall summary scores, the Physical Component Summary (PCS) and the Mental Component Summary (MCS) also can be computed. The SF-36 has proven useful in monitoring general and specific populations, comparing the relative burden of different disease, differentiating the health benefits produced by different treatments, and in screening individual patients. The purpose of the SF-36 in this study was to assess the HRQoL of patients. Given the nature of this disease and the 4-weekly assessment, the SF-36 version 2, with a 4-week recall period, was used in this study.</description>
        <time_frame>Baseline, Week 24</time_frame>
        <population>Full Analysis Set (FAS)</population>
        <group_list>
          <group group_id="O1">
            <title>Erenumab</title>
            <description>70 mg and 140 mg Erenumab</description>
          </group>
          <group group_id="O2">
            <title>Topiramate</title>
            <description>Topiramate in the highest tolerated dose (50 - 100 mg/day)</description>
          </group>
        </group_list>
        <measure>
          <title>EXPLORATORY ENDPOINT: Proportion of Patients Achieving at Least a 5 Points Increase in the Medical Outcome Short Form Health Survey Version 2 (SF-36) From Baseline to Week 24</title>
          <description>The SF-36 is a widely used and extensively studied instrument to measure health-related quality of life (HRQoL) among healthy subjects and patients with acute and chronic conditions. It consists of eight subscales that can be scored individually: Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional, and Mental Health. Two overall summary scores, the Physical Component Summary (PCS) and the Mental Component Summary (MCS) also can be computed. The SF-36 has proven useful in monitoring general and specific populations, comparing the relative burden of different disease, differentiating the health benefits produced by different treatments, and in screening individual patients. The purpose of the SF-36 in this study was to assess the HRQoL of patients. Given the nature of this disease and the 4-weekly assessment, the SF-36 version 2, with a 4-week recall period, was used in this study.</description>
          <population>Full Analysis Set (FAS)</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="388"/>
                <count group_id="O2" value="388"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Physical Component Summary (PCS)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="185"/>
                    <measurement group_id="O2" value="145"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Mental Component Summary (MCS)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="98"/>
                    <measurement group_id="O2" value="65"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Physical Component Summary (PCS)</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>Regression, Logistic</method>
            <method_desc>Odds ratio is obtained from a logistic regression model that includes treatment group and stratification factor (MMD at baseline)</method_desc>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>1.75</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.26</ci_lower_limit>
            <ci_upper_limit>2.43</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Mental Component Summary (MCS)</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.005</p_value>
            <method>Regression, Logistic</method>
            <method_desc>Odds ratio is obtained from a logistic regression model that includes treatment group and stratification factor (MMD at baseline)</method_desc>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>1.79</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.29</ci_lower_limit>
            <ci_upper_limit>2.69</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were collected from first dose of study treatment until 8 weeks after the last Investigational Medicinal product (IMP) injection, assessed up to approximately 33 weeks (treatment duration ranged from 4.0 to 25.1 weeks).</time_frame>
      <desc>Any sign or symptom that occurs during the study treatment until 8 weeks after the last Investigational Medicinal product (IMP) injection. Maximum exposure to study treatments = 25 weeks (Erenumab treatment group) and 25.1 weeks (Topiramate treatment group).</desc>
      <group_list>
        <group group_id="E1">
          <title>Erenumab</title>
          <description>70 mg and 140 mg Erenumab</description>
        </group>
        <group group_id="E2">
          <title>Topiramate</title>
          <description>Topiramate in the highest tolerated dose (50 - 100 mg/day)</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (23.1)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="388"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="388"/>
                <counts group_id="E2" subjects_affected="19" subjects_at_risk="388"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Angle closure glaucoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="388"/>
              </event>
              <event>
                <sub_title>Retinal detachment</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="388"/>
              </event>
              <event>
                <sub_title>Rhegmatogenous retinal detachment</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="388"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Gastritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="388"/>
              </event>
              <event>
                <sub_title>Irritable bowel syndrome</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="388"/>
              </event>
              <event>
                <sub_title>Mechanical ileus</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="388"/>
              </event>
              <event>
                <sub_title>Obstructive defaecation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="388"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Cholelithiasis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="388"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaphylactic shock</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="388"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Appendicitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="388"/>
              </event>
              <event>
                <sub_title>Bacteriuria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="388"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="388"/>
              </event>
              <event>
                <sub_title>Gastrointestinal infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="388"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="388"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="388"/>
              </event>
              <event>
                <sub_title>Papilloma viral infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="388"/>
              </event>
              <event>
                <sub_title>Parasitic gastroenteritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="388"/>
              </event>
              <event>
                <sub_title>Pyelonephritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="388"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Ankle fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="388"/>
              </event>
              <event>
                <sub_title>Concussion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="388"/>
              </event>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="388"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="388"/>
              </event>
              <event>
                <sub_title>Ligament rupture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="388"/>
              </event>
              <event>
                <sub_title>Limb injury</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="388"/>
              </event>
              <event>
                <sub_title>Skin laceration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="388"/>
              </event>
              <event>
                <sub_title>Sternal fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="388"/>
              </event>
              <event>
                <sub_title>Tendon injury</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="388"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="388"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="388"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Intervertebral disc protrusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="388"/>
              </event>
              <event>
                <sub_title>Lumbar spinal stenosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="388"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Fibroadenoma of breast</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="388"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Migraine</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="388"/>
              </event>
              <event>
                <sub_title>Migraine with aura</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="388"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="388"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="388"/>
              </event>
              <event>
                <sub_title>Major depression</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="388"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Cervical dysplasia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="388"/>
              </event>
              <event>
                <sub_title>Dysmenorrhoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="388"/>
              </event>
              <event>
                <sub_title>Endometriosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="388"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA (23.1)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="253" subjects_at_risk="388"/>
                <counts group_id="E2" subjects_affected="331" subjects_at_risk="388"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Vertigo</sub_title>
                <counts group_id="E1" subjects_affected="20" subjects_at_risk="388"/>
                <counts group_id="E2" subjects_affected="24" subjects_at_risk="388"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" subjects_affected="22" subjects_at_risk="388"/>
                <counts group_id="E2" subjects_affected="23" subjects_at_risk="388"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="48" subjects_at_risk="388"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="388"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="20" subjects_at_risk="388"/>
                <counts group_id="E2" subjects_affected="29" subjects_at_risk="388"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="36" subjects_at_risk="388"/>
                <counts group_id="E2" subjects_affected="71" subjects_at_risk="388"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="44" subjects_at_risk="388"/>
                <counts group_id="E2" subjects_affected="74" subjects_at_risk="388"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="145" subjects_at_risk="388"/>
                <counts group_id="E2" subjects_affected="150" subjects_at_risk="388"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="388"/>
                <counts group_id="E2" subjects_affected="22" subjects_at_risk="388"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="388"/>
                <counts group_id="E2" subjects_affected="39" subjects_at_risk="388"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="21" subjects_at_risk="388"/>
                <counts group_id="E2" subjects_affected="20" subjects_at_risk="388"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Disturbance in attention</sub_title>
                <counts group_id="E1" subjects_affected="18" subjects_at_risk="388"/>
                <counts group_id="E2" subjects_affected="63" subjects_at_risk="388"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="28" subjects_at_risk="388"/>
                <counts group_id="E2" subjects_affected="60" subjects_at_risk="388"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="388"/>
                <counts group_id="E2" subjects_affected="23" subjects_at_risk="388"/>
              </event>
              <event>
                <sub_title>Paraesthesia</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="388"/>
                <counts group_id="E2" subjects_affected="159" subjects_at_risk="388"/>
              </event>
              <event>
                <sub_title>Taste disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" subjects_affected="26" subjects_at_risk="388"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Sleep disorder</sub_title>
                <counts group_id="E1" subjects_affected="20" subjects_at_risk="388"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="388"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Study Director</name_or_title>
      <organization>Novartis Pharmaceuticals</organization>
      <phone>862-778-8300</phone>
      <email>Novartis.email@novartis.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03828539
org study id: CAMG334ADE01
secondary id: 2018-000943-15
nct id: NCT03828539
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
This study used a single-cohort, 2-treatment arm, parallel-group randomized, double-blind,
      double-dummy design in adult patients with episodic migraine and chronic migraine, who had to
      be either naïve or not suitable for or could have failed up to three prophylactic treatments
      out of: propranolol/metoprolol, amitriptyline, flunarizine. Patients were stratified into
      groups according to their number of migraine days during the baseline period.
All patients completing the Baseline period and fulfilling baseline eligibility criteria were
      invited to participate to the Double-blind, double-dummy Treatment Epoch (DBTE, 24 weeks) .

      Eligible patients were randomized to one of two treatment arms. DBTE started with a titration
      phase for topiramate of a maximum of 6 weeks to determine the maximal tolerated dose and
      aimed to reach the recommended treatment dose of 100 mg according to the German SmPC. After
      the titration phase, maintenance phase started (18 weeks). Topiramate dose had to be
      maintained until the end of the DBTE. Erenumab dose at beginning of the DBTE was determined
      patient individually by the investigator based on the guidance provided in the SmPC and was
      either 70 mg or 140 mg. Dose escalation from 70 mg to 140 mg in case of insufficient response
      was considered at anytime during the DBTE.

      Dose reduction of topiramate and erenumab was not allowed during DBTE (Week 0 to Week 24).
      After Week 24 or if the patient discontinued study drug, a one week double-blind taper off
      phase followed to ensure proper down titration for topiramate. At the end of the DBTE (24
      weeks) the final assessment occurred to address the objectives.

      A Follow-Up Visit 4 weeks after last study visit (or 8 weeks after last IMP injection for
      discontinued patients) was required as part of routine safety monitoring. The primary
      analysis was triggered when all patients had completed their respective last visit of the
      DBTE.

      The End of study occurred when the last patient completed last visit (LPLV).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Double (Participant, Investigator)
measure: Proportion of Patients With Treatment Discontinuation Due to an Adverse Event (AE) During the Double-blind Treatment Epoch/Period (DBTE)
time frame: 24 Weeks
description: The primary objective was to demonstrate the tolerability of 70 mg and 140 mg erenumab compared to topiramate in the highest tolerated dose assessed by the rate of patients discontinuing treatment due to AE during the double-blind epoch of the study.
measure: Number of Patients With at Least 50% Reduction From Baseline in Monthly Migraine Days (MMD) Over the Last Three Months (Month 4, 5, and 6)
time frame: Baseline, Last three months (month 4, 5, and 6)
description: The secondary objective of this study was to evaluate the effect of erenumab compared to topiramate on the proportion of patients with at least 50% reduction from baseline in MMDs. The Baseline period was defined as the period between Week -4 and the day prior to first dose. This was analyzed by logistic regression over the last 3 months (months 4, 5, and 6) of treatment. All the subjects' data collected regarding 50% response in MMD was used in the analysis regardless of whether subjects discontinue study treatment or not. Subjects with missing response information on this endpoint were imputed as non-response (non-responder imputation).
measure: EXPLORATORY ENDPOINT: Proportion of Patients Achieving at Least a 5 Points Reduction in the Headache Impact Test (HIT-6) From Baseline to Week 24
time frame: Baseline, Week 24
description: The HIT-6 is a widely used patient-reported outcome measure that assesses the negative effects of headaches on normal activity. Six items assess the frequency of pain severity, headaches limiting daily activity (household, work, school, and social), wanting to lie down when headache is experienced, feeling too tired to work or do daily activities because of headache, feeling "fed up" or irritated because of headache, and headaches limiting ability to concentrate or work on daily activities. Each of the 6 questions is responded to using 1 of 5 response categories: "never," "rarely," "sometimes," "very often," or "always." For each HIT-6 item, 6, 8, 10, 11, or 13 points, respectively, are assigned to the response provided. These points are summed to produce a total HIT-6 score that ranges from 36 to 78. HIT-6 scores are categorized into 4 grades: little or no impact (49 or less), some impact (50 - 55), substantial impact (56 - 59), and severe impact (60 - 78) due to headache.
measure: EXPLORATORY ENDPOINT: Proportion of Patients Achieving at Least a 5 Points Increase in the Medical Outcome Short Form Health Survey Version 2 (SF-36) From Baseline to Week 24
time frame: Baseline, Week 24
description: The SF-36 is a widely used and extensively studied instrument to measure health-related quality of life (HRQoL) among healthy subjects and patients with acute and chronic conditions. It consists of eight subscales that can be scored individually: Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional, and Mental Health. Two overall summary scores, the Physical Component Summary (PCS) and the Mental Component Summary (MCS) also can be computed. The SF-36 has proven useful in monitoring general and specific populations, comparing the relative burden of different disease, differentiating the health benefits produced by different treatments, and in screening individual patients. The purpose of the SF-36 in this study was to assess the HRQoL of patients. Given the nature of this disease and the 4-weekly assessment, the SF-36 version 2, with a 4-week recall period, was used in this study.
arm group label: Erenumab
arm group type: Experimental
description: 70 mg and 140 mg Erenumab
arm group label: Topiramate
arm group type: Active Comparator
description: Topiramate in the highest tolerated dose (50 - 100 mg/day)
intervention type: Biological
intervention name: Erenumab
description: 70mg/1mL (70 mg) or 2x70mg/1mL (140 mg) in pre-filled syringe, administered every 4 weeks
arm group label: Erenumab
other name: AMG334
intervention type: Drug
intervention name: Topiramate
description: Film-coated tablet taken orally:
25 mg administered once daily (first week of titration phase). After the first week, titration was done according to the summary of product characteristics (SmPC) in 25 mg increments each week and aimed to reach the recommended daily treatment dose of 100 mg (50/75/100 mg). 50/75/100 mg were administered twice daily during titration phase and maintenance phase.
arm group label: Topiramate
other name: Topamax
intervention type: Biological
intervention name: Erenumab matching placebo
description: Erenumab matching placebo pre-filled syringue administered every 4 weeks
arm group label: Erenumab
intervention type: Drug
intervention name: Topiramate matching placebo
description: Topiramate matching placebo administered daily
arm group label: Topiramate
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Novartis Pharmaceuticals
role: Study Director
affiliation: Novartis Pharmaceuticals
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Germany
url: https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=941
description: A Plain Language Trial Summary is available on novartisclinicaltrials.com
responsible party type: Sponsor
mesh term: Migraine Disorders
mesh term: Topiramate
mesh term: Erenumab
mesh term: Antibodies, Monoclonal
sharing ipd: Yes
ipd description: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 