Comparative Study of Oral Atogepant Versus Oral Topiramate to Assess Adverse Events in Adult Participants With Migraine (ATO-TOPIRAMATE)

A Randomized, Double-Blind, Parallel-Group, Active Controlled Trial With Open-Label Safety Extension to Evaluate the Tolerability, Safety, and Efficacy of Atogepant Versus Topiramate in Subjects Requiring Preventive Treatment of Migraine (TEMPLE)

A migraine is a moderate to severe headache on one side of the head that may be accompanied by throbbing, nausea, vomiting, sensitivity to light and sound, or other symptoms. The main goal of the study is to evaluate the tolerability (how patients handle the study treatment) and safety of atogepant compared to topiramate in participants with migraine.

Atogepant is a medicine currently approved for the preventive treatment of adult patients with episodic migraine (0 to 14 migraine days per month) and is being studied for the preventative treatment of migraine globally. Topiramate is an approved medication for migraine prevention. This study is conducted in 2 periods. In Period 1, participants will be randomly put into 1 of 2 groups at the start of the study to receive atogepant or topiramate. In Period 2, eligible participants will receive atogepant. Approximately 520 participants aged 18 and older will be enrolled in this study in approximately 85 sites across the world.

Participants will receive atogepant (and placebo for topiramate) or topiramate (and placebo for atogepant) for 24 weeks in Period 1. Both atogepant and placebo for atogepant are given as a tablet to take by mouth while topiramate and placebo for topiramate are given as a capsule to take by mouth. After 24 weeks, all eligible participants will receive atogepant for 52 weeks in Period 2. Participants are monitored for safety for 4 weeks after their last study treatment.

There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The safety and tolerability of the treatment will be checked by medical assessments, blood tests, checking for adverse events and completing questionnaires.

Study Overview

• Status: Active, not recruiting
• Conditions: Migraine
• Intervention / Treatment: Drug: Atogepant; Drug: Placebo for Topiramate; Drug: Placebo for Atogepant; Drug: Topiramate

• Study Type: Interventional
• Enrollment (Actual): 545
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Oberoesterreich
    • Linz, Oberoesterreich, Austria, 4021
      • Konventhospital Barmherzige Brueder Linz /ID# 247217
  • Tirol
    • Innsbruck, Tirol, Austria, 6020
      • Medizinische Universitaet Innsbruck /ID# 247213
  • Wien
    • Vienna, Wien, Austria, 1090
      • Medizinische Universitaet Wien /ID# 247119
• Belgium
  • Brugge, Belgium, 8000
    • AZ Sint-Jan Brugge /ID# 246962
  • Liege, Belgium, 4000
    • CHR de la Citadelle /ID# 246964
  • Bruxelles-Capitale
    • Jette, Bruxelles-Capitale, Belgium, 1090
      • Universitair Ziekenhuis Brussel /ID# 246959
  • Limburg
    • Hasselt, Limburg, Belgium, 3500
      • Jessa Ziekenhuis /ID# 246954
  • Oost-Vlaanderen
    • Gent, Oost-Vlaanderen, Belgium, 9000
      • UZ Gent /ID# 246957
• Canada
  • British Columbia
    • Victoria, British Columbia, Canada, V8R 1J8
      • Vancouver Island Health Authority /ID# 247733
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3R 1V9
      • Maritime Neurology /ID# 247728
  • Ontario
    • Brampton, Ontario, Canada, L6T 0G1
      • Aggarwal and Associates Limited /ID# 247727
• Czechia
  • Hradec Kralove, Czechia, 500 09
    • NeuroHK s.r.o. /ID# 247500
  • Pardubice, Czechia, 530 02
    • Pratia Pardubice a.s. /ID# 249017
  • Prague, Czechia, 130 00
    • Pratia Prague s.r.o. /ID# 245925
  • Prague 10, Czechia, 100 00
    • Clintrial s.r.o. /ID# 245926
  • Praha, Czechia, 140 59
    • Fakultni Thomayerova nemocnice /ID# 249016
  • Praha, Czechia, 186 00
    • INEP medical s.r.o. /ID# 245927
  • Ostrava-mesto
    • Ostrava, Ostrava-mesto, Czechia, 702 00
      • CCR Ostrava, s.r.o. /ID# 245924
  • Plzensky Kraj
    • Plzen, Plzensky Kraj, Czechia, 301 00
      • A-Shine s.r.o. /ID# 245923
  • Praha 5
    • Prague, Praha 5, Czechia, 150 00
      • Praglandia /ID# 247511
• France
  • Clermont Ferrand, France, 63000
    • CHU Clermont Ferrand - Hopital Gabriel Montpied /ID# 247561
  • Paris, France, 75010
    • AP-HP - Groupe Hospitalier 10e - Hopital Lariboisiere /ID# 249244
  • Rhone
    • Bron, Rhone, France, 69500
      • Hospices Civils de Lyon (HCL) - Hopital Louis Pradel /ID# 247562
• Germany
  • Berlin, Germany, 10713
    • Neurologisches Facharztzentrum Berlin /ID# 248064
  • Berlin, Germany, 13353
    • Charite Universitaetsklinikum Berlin - Campus Virchow /ID# 246029
  • Bielefeld, Germany, 33647
    • NeuroZentrum Bielefeld /ID# 250758
  • Erbach, Germany, 64711
    • Neuro Centrum Odenwald /ID# 248067
  • Essen, Germany, 45147
    • Universitaetsklinikum Essen /ID# 246033
  • Greifswald, Germany, 17475
    • Universitaetsmedizin Greifswald /ID# 248574
  • Hamburg, Germany, 20253
    • Klinische Forschung Hamburg GmbH /ID# 248620
  • Kassel, Germany, 34121
    • Neurologische Gemeinschaftspraxis Kassel und Vellmar /ID# 248085
  • Stuttgart, Germany, 70178
    • Lewis Neurologie /ID# 250498
  • Baden-Wuerttemberg
    • Boeblingen, Baden-Wuerttemberg, Germany, 71034
      • Studienzentrum fuer Neurologie und Psychiatrie /ID# 249236
    • Tubingen, Baden-Wuerttemberg, Germany, 72076
      • Universitaetsklinikum Tuebingen /ID# 246043
    • Ulm, Baden-Wuerttemberg, Germany, 89073
      • Neuropoint GmbH /ID# 246038
  • Bayern
    • Unterhaching, Bayern, Germany, 82008
      • Neuropraxis Muenchen Sued /ID# 246045
  • Brandenburg
    • Hoppegarten, Brandenburg, Germany, 15366
      • Gesundheitszentrum Hoppegarten /ID# 249242
  • Hessen
    • Bad Homburg, Hessen, Germany, 61348
      • Praxis fuer Neurologie, Psychiatrie und Psychotherapie /ID# 248427
    • Frankfurt am Main, Hessen, Germany, 65929
      • Kopfschmerzzentrum - Frankfurt /ID# 248686
  • Mecklenburg-Vorpommern
    • Schwerin, Mecklenburg-Vorpommern, Germany, 19055
      • Klinische Forschung Schwerin GmbH /ID# 248074
  • Niedersachsen
    • Hannover, Niedersachsen, Germany, 30159
      • Klinische Forschung Hannover-Mitte GmbH /ID# 248565
    • Westerstede, Niedersachsen, Germany, 26655
      • Studienzentrum Nord-West /ID# 246039
  • Nordrhein-Westfalen
    • Siegen, Nordrhein-Westfalen, Germany, 57076
      • ZNS Siegen /ID# 251180
  • Rheinland-Pfalz
    • Trier, Rheinland-Pfalz, Germany, 54292
      • Krankenhaus der Barmherzigen Brüder Trier /ID# 248564
  • Sachsen
    • Chemnitz, Sachsen, Germany, 09111
      • Pharmakologisches Studienzentrum Chemnitz GmbH /ID# 246030
    • Dresden, Sachsen, Germany, 01307
      • Universitaetsklinikum Carl Gustav Carus Dresden /ID# 246040
    • Leipzig, Sachsen, Germany, 04107
      • Ambenet Hausarztpraxis /ID# 246028
  • Schleswig-Holstein
    • Kiel, Schleswig-Holstein, Germany, 24149
      • Schmerzklinik Kiel /ID# 246037
• Hungary
  • Budapest, Hungary, 1033
    • Clinexpert Kft /ID# 247868
  • Budapest, Hungary, 1138
    • S-Medicon Kft /ID# 247682
  • Budapest, Hungary, 1085
    • Semmelweis Egyetem /ID# 248428
  • Budapest, Hungary, 1024
    • MIND Clinic /ID# 247867
  • Debrecen, Hungary, 4025
    • Debreceni Egeszsegugyi Kozpontja /ID# 247549
• Israel
  • H_efa
    • Hadera, H_efa, Israel, 38100
      • Hillel Yaffe Medical Center /ID# 247258
  • HaDarom
    • Be'er Sheva, HaDarom, Israel, 8410101
      • Soroka University Medical Center /ID# 247260
  • HaMerkaz
    • Kfar Saba, HaMerkaz, Israel, 4428164
      • Meir Medical Center /ID# 247261
  • Yerushalayim
    • Jerusalem, Yerushalayim, Israel, 91031
      • Shaare Zedek Medical Center /ID# 247259
• Italy
  • Modena, Italy, 41124
    • Azienda Ospedaliero-Universitaria di Modena /ID# 247578
  • Pavia, Italy, 27100
    • Fondazione Mondino Istituto Neurologico Nazionale a Carattere Scientifico IRCCS /ID# 247579
  • Roma, Italy, 00128
    • Fondazione Policlinico Universitario Campus Bio-Medico /ID# 247580
  • Firenze
    • Florence, Firenze, Italy, 50134
      • Azienda Ospedaliero Universitaria Careggi /ID# 247575
  • Napoli
    • Naples, Napoli, Italy, 80138
      • Azienda Ospedaliera Universitaria Luigi Vanvitelli /ID# 247576
  • Roma
    • Rome, Roma, Italy, 00163
      • IRCCS San Raffaele /ID# 247573
• Poland
  • Kujawsko-pomorskie
    • Bydgoszcz, Kujawsko-pomorskie, Poland, 85-079
      • Vitamed Galaj i Cichomski Sp.j. /ID# 247314
    • Bydgoszcz, Kujawsko-pomorskie, Poland, 85-752
      • Athleticomed Sp. z o.o /ID# 250790
  • Lubelskie
    • Lublin, Lubelskie, Poland, 20-582
      • Indywidualna Praktyka Lekarska dr hab. med. Anna Szczepanska-Szerej /ID# 247298
  • Malopolskie
    • Oświęcim, Malopolskie, Poland, 32-600
      • Instytut Zdrowia Dr Boczarska Jedynak /ID# 247315
  • Mazowieckie
    • Sochaczew, Mazowieckie, Poland, 96-500
      • RCMed Oddzial Sochaczew /ID# 247378
    • Warsaw, Mazowieckie, Poland, 02-677
      • ETG Neuroscience Sp. z o.o. /ID# 247331
  • Slaskie
    • Katowice, Slaskie, Poland, 40-282
      • Silmedic Sp. z o.o. /ID# 247376
  • Wielkopolskie
    • Poznan, Wielkopolskie, Poland, 60-529
      • Solumed Centrum Medyczne /ID# 247317
    • Poznan, Wielkopolskie, Poland, 61-731
      • Clinical Research Center Sp. z.o.o. Medic-R sp. k /ID# 247323
• Portugal
  • Braga, Portugal, 4710-243
    • 2CA-Braga, Hospital de Braga /ID# 247165
  • Lisboa, Portugal, 1500-650
    • Hospital da Luz Lisboa /ID# 247168
  • Lisboa, Portugal, 2720-276
    • Hospital Prof. Doutor Fernando Fonseca, EPE /ID# 247172
  • Lisboa, Portugal, 1649-035
    • Unidade Local de Saude de Santa Maria, EPE /ID# 247167
  • Matosinhos, Portugal, 4464-513
    • Unidade Local de Saúde de Matosinhos, EPE /ID# 247169
  • Setubal
    • Almada, Setubal, Portugal, 2805-267
      • Hospital Garcia de Orta /ID# 247163
• United Kingdom
  • Bristol, United Kingdom, BS37 4AX
    • West Walk Surgery /ID# 252855
  • Dorset
    • Poole, Dorset, United Kingdom, BH15 4JQ
      • The Adam Practice /ID# 248880
  • Scotland
    • Glasgow, Scotland, United Kingdom, G12 0XH
      • Duplicate_NHS Greater Glasgow and Clyde /ID# 247979

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Documented history of migraine (with or without aura) for >= 12 months prior to screening (Visit 1).
• History of >= 4 migraine days per month who require preventive treatment of migraine and are eligible for conventional migraine prophylaxis.

Exclusion Criteria:

• Have used topiramate or atogepant in the past.
• Have clinically significant cardiovascular, cerebrovascular, hematologic, endocrine, pulmonary, renal, hepatic, gastrointestinal, or neurologic disease.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Atogepant; Participants will receive atogepant in double-blind period. From Week 25, eligible participants will receive atogepant in open-label period.	Drug: Atogepant; Oral Tablet; Other Names: QULIPTA; Drug: Placebo for Topiramate; Oral Capsule
Active Comparator: Topiramate; Participants will receive topiramate in double-blind period. From Week 25, eligible participants will receive atogepant in open-label period.	Drug: Atogepant; Oral Tablet; Other Names: QULIPTA; Drug: Placebo for Atogepant; Oral Tablet; Drug: Topiramate; Oral Capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Discontinued Treatment due to Adverse Events (AEs)	An AE is any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.	Up to Week 24 (Double-blind treatment period)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving >= 50% Improvement (Reduction) in Mean Monthly Migraine Days Based on mITT Population.	Improvement in mean monthly migraine days will be assessed.	Month 4 to Month 6 (Double-blind treatment period)
Change From Baseline in Mean Monthly Migraine Days	A migraine day is defined as any calendar day on which a headache occurs which meets criteria listed, as per participant eDiary.	Month 4 to Month 6 (Double-blind treatment period)
Change from Baseline in HIT-6 (Headache Impact Test) Total Score	The HIT-6 is a self-report questionnaire designed to evaluate the impact of headache on quality of life. Responses are based on frequency using a 5-point scale ranging from "never" to "always." The HIT-6 total score (which ranges from 36 to 78) is the sum of the responses, each of which is assigned a score ranging from 6 points (never) to 13 points (always).	At Week 24
Change From Baseline in Migraine Specific Quality of Life Questionnaire, Version 2.1 (MSQ v2.1) Role Function-Restrictive Domain Score	MSQ v2.1 is a 14-item questionnaire designed to measure health-related quality of life impairments attributed to migraine in the past 4 weeks. It is divided into three domains: Role Function Restrictive, Role Function Preventive, and Emotional Function domain. Participants respond to items using a 6-point scale ranging from "none of the time" to "all of the time." Raw dimension scores are computed as a sum of item responses and rescaled to a 0 to 100 scale, where higher scores indicate better quality of life.	At Week 24
Percentage of Participants Achieving a Rating of "Much Better" or "Very Much Better" Assessed by the Patient Global Impression of Change (PGIC)	The PGIC is a single item used to measure the participants impression of overall change in migraine since the first dose of study medication. The measure uses a 7-point rating scale with responses ranging from "very much better" to "very much worse."	At Week 24
Change from baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) Cognitive Function -Abilities Subset -Short Form 6a Version 2.0 score.	The Patient Reported Outcomes Measurement Information System (PROMIS®) Cognitive Function and Cognitive Function Abilities Subset item banks assess participant perceived cognitive deficits. Facets include mental acuity, concentration, verbal and nonverbal memory, verbal fluency, and perceived changes in these cognitive functions. The extent to which cognitive impairments interfere with daily functioning, whether other people observe cognitive impairments, and the impact of cognitive dysfunction on quality of life are also assessed. (Subset of participants when and where available)	At Week 6

Collaborators and Investigators

• Sponsor: AbbVie
• Investigators: Study Director: ABBVIE INC., AbbVie

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): October 7, 2023
• Primary Completion (Actual): April 28, 2025
• Study Completion (Estimated): May 1, 2026

Study Registration Dates

• First Submitted: February 20, 2023
• First Submitted That Met QC Criteria: February 20, 2023
• First Posted (Actual): February 28, 2023

Study Record Updates

• Last Update Posted (Actual): May 25, 2025
• Last Update Submitted That Met QC Criteria: May 21, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Migraine; Episodic migraine; Chronic migraine; Atogepant; QULIPTA; Migraine prophylaxis; Topiramine
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders; Physiological Effects of Drugs; Hypoglycemic Agents; Anticonvulsants; Topiramate
• Other Study ID Numbers: M22-061; 2022-501172-25-00 (Other Identifier: EU CT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: AbbVie is committed to responsible clinical trial data sharing. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information.
• IPD Sharing Time Frame: For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/
• IPD Sharing Access Criteria: To learn more about the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No