Efficacy, Safety, and Tolerability of Atogepant for the Prevention of Chronic Migraine

A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy, Safety, and Tolerability of Atogepant for the Prevention of Chronic Migraine (Progress)

This study evaluated the efficacy, safety and tolerability of atogepant in participants with chronic migraine. This study included a 12-week treatment period.

Study Overview

• Status: Completed
• Conditions: Chronic Migraine
• Intervention / Treatment: Drug: Atogepant 60 mg; Drug: Atogepant 30 mg; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 778
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • St Leonards, New South Wales, Australia, 2065
      • Royal North Shore Hospital /ID# 237008
  • Victoria
    • Parkville, Victoria, Australia, 3050
      • The Royal Melbourne Hospital /ID# 236859
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T3M 1M4
      • CHAMP Clinic /ID# 236252
  • British Columbia
    • Victoria, British Columbia, Canada, V8R 1J8
      • Vancouver Island Health Authority /ID# 238053
  • Ontario
    • Ottawa, Ontario, Canada, K2G 6E2
      • Ottawa Headache Centre Research Inc /ID# 236432
  • Quebec
    • Montreal, Quebec, Canada, H2W 1V1
      • Clinique des cephalees de Montreal /ID# 236266
    • Montreal, Quebec, Canada, H3A 2B4
      • Montreal Neurological Institut /ID# 236329
• China
  • Beijing, China, 100032
    • Beijing Friendship Hospital /ID# 237264
  • Suzhou, China, 215004
    • The Second Hospital of Soochow University /ID# 234296
  • Tianjin, China, 300350
    • Tianjin Huanhu Hospital (THH) /ID# 236524
  • Wuhan, China, 430030
    • Tongji Hospital Tongji Medical College of HUST /ID# 237835
  • Beijing
    • Beijing, Beijing, China, 100191
      • Peking University Third Hospital /ID# 238150
    • Beijing, Beijing, China, 100853
      • Chinese PLA General Hospital /ID# 238237
  • Guangdong
    • Guangzhou, Guangdong, China, 510260
      • The Second Affiliated Hospital of Guangzhou Medical University /ID# 238133
    • Guangzhou, Guangdong, China, 510180
      • Guangzhou First People's Hospital /ID# 236510
  • Hebei
    • Wuhan, Hebei, China, 430060
      • Hubei General Hospital /ID# 236486
  • Henan
    • Zhengzhou, Henan, China, 450052
      • The First Affiliated Hospital of Zhengzhou University /ID# 237025
  • Jiangsu
    • Nanjing, Jiangsu, China, 210029
      • Jiangsu Province Hospital /ID# 237846
  • Jilin
    • Changchun, Jilin, China, 130022
      • The Second Hospital of Jilin University /ID# 236520
  • Shanghai
    • Shanghai, Shanghai, China, 200065
      • Ruijin Hospital, Shanghai Jiaotong University School of Medicine /ID# 237847
  • Shanxi
    • Taiyuan, Shanxi, China, 030000
      • The Second Hospital of Shanxi Medical University /ID# 236529
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310009
      • The second Affiliated hospital of Zhejiang University school of Medicine /ID# 238260
    • Hangzhou, Zhejiang, China, 310020
      • Sir Run Run Shaw Hospital Zhejiang University School of Medicine /ID# 236500
• Czechia
  • Hradec Kralove, Czechia, 500 09
    • NEUROHK s.r.o. /ID# 236290
  • Kladno, Czechia, 272 01
    • BRAIN-SOULTHERAPY s.r.o. /ID# 236380
  • Ostrava, Czechia, 702 00
    • CCR Ostrava, s.r.o. /ID# 234291
  • Prague, Czechia, 160 00
    • FORBELI s.r.o. /ID# 236427
  • Prague 10, Czechia, 100 00
    • CLINTRIAL s.r.o. /ID# 237793
  • Prague 4, Czechia, 140 00
    • CCR Czech a.s /ID# 236249
  • Praha, Czechia, 130 00
    • CCR Prague s.r.o. /ID# 236250
  • Praha, Czechia, 140 59
    • Thomayerova nemocnice /ID# 237175
  • Zlin, Czechia, 760 01
    • NeuroMed Zlin s.r.o. /ID# 236416
• Denmark
  • Hovedstaden
    • Glostrup, Hovedstaden, Denmark, 2600
      • Rigshospitalet Glostrup /ID# 236411
• France
  • Bron, France, 69677
    • Hôpital Pierre Wertheimer /ID# 236969
  • Clermont Ferrand, France, 63000
    • CHU Gabriel Montpied /ID# 237323
  • Bouches-du-Rhone
    • Marseille CEDEX 05, Bouches-du-Rhone, France, 13385
      • AP-HM - Hopital de la Timone /ID# 236285
  • Haute-Savoie
    • PRINGY cedex, Haute-Savoie, France, 74374
      • CH Annecy Genevois Site Annecy /ID# 236385
• Germany
  • Berlin, Germany, 13353
    • Charite Universitaetsklinikum Berlin - Campus Virchow /ID# 237256
  • Essen, Germany, 45133
    • Praxis Dr. Gendolla /ID# 236311
  • Essen, Germany, 45147
    • Universitaetsklinikum Essen /ID# 237209
  • Hamburg, Germany, 20251
    • CTC North GmbH & Co. KG /ID# 236328
  • Kassel, Germany, 34131
    • Vitos Orthopaedische Klinik Kassel gemeinnuetzige GmbH /ID# 236723
  • Kiel, Germany, 24149
    • Schmerzklinik Kiel /ID# 236444
  • München, Germany, 81377
    • LMU Klinikum Campus Grosshadern /ID# 236293
• Italy
  • Bari, Italy, 70124
    • Azienda Ospedaliera Universitaria Consorziale Policlinico /ID# 237492
  • Florence, Italy, 50134
    • Azienda Ospedaliero Universitaria Careggi /ID# 237598
  • Milan, Italy, 20133
    • Fondazione IRCCS Istituto Neurologico Carlo Besta /ID# 237291
  • Napoli, Italy, 80138
    • AOU Universita degli Studi della Campania Luigi Vanvitelli /ID# 236361
  • Pavia, Italy, 27100
    • Universita di Pavia /ID# 236363
  • Rome, Italy, 00163
    • IRCCS San Raffaele Pisana /ID# 236552
• Japan
  • Hiroshima, Japan, 730-0031
    • DOI Internal Medicine-Neurology Clinic /ID# 234562
  • Hiroshima, Japan, 732-0822
    • Hiroshima Neurology Clinic /ID# 234563
  • Kagoshima, Japan, 892-0844
    • Tanaka Neurosurgical clinic /ID# 234760
  • Kyoto, Japan, 600-8811
    • Tatsuoka Neurology Clinic /ID# 234782
  • Osaka, Japan, 556-0017
    • Tominaga Hospital /ID# 234781
  • Tokyo, Japan, 108-0075
    • Shinagawa Strings Clinic /ID# 234780
  • Ehime
    • Matsuyama-shi, Ehime, Japan, 790-0925
      • Takanoko Hospital /ID# 234564
  • Fukui
    • Fukui-shi, Fukui, Japan, 918-8235
      • Fukuiken Saiseikai Hospital /ID# 236794
  • Hokkaido
    • Sapporo-shi, Hokkaido, Japan, 003-0003
      • Higashi Sapporo Neurology and Neurosurgery Clinic /ID# 234549
  • Hyogo
    • Kobe-shi, Hyogo, Japan, 658-0064
      • Konan Medical Center /ID# 236230
  • Kagoshima
    • Kagoshima-shi, Kagoshima, Japan, 892-0842
      • Atsuchi Neurosurgical Hospital /ID# 234779
  • Kanagawa
    • Isehara-shi, Kanagawa, Japan, 259-1193
      • Tokai University Hospital /ID# 237595
    • Kawasaki-shi, Kanagawa, Japan, 211-8588
      • Fujitsu Clinic /ID# 237443
  • Kochi
    • Kochi-shi, Kochi, Japan, 780-8011
      • Umenotsuji Clinic /ID# 234495
  • Miyagi
    • Sendai-shi, Miyagi, Japan, 982-0014
      • Sendai Headache and Neurology Clinic Medical Corporation /ID# 234496
  • Saitama
    • Iruma-gun, Saitama, Japan, 350-0495
      • Saitama Medical University Hospital /ID# 237019
    • Saitama-shi, Saitama, Japan, 338-8577
      • Saitama Neuropsychiatric Institute /Id# 234550
  • Shizuoka
    • Shizuoka-shi, Shizuoka, Japan, 420-0853
      • Japanese Red Cross Shizuoka Hospital /ID# 234372
  • Tochigi
    • Shimotsuga-gun, Tochigi, Japan, 321-0293
      • Dokkyo Medical University Hospital /ID# 236810
  • Tokyo
    • Chofu-shi, Tokyo, Japan, 182-0006
      • Niwa Family Clinic /ID# 234552
    • Shibuya-ku, Tokyo, Japan, 151-0051
      • Tokyo Headache Clinic /ID# 234555
    • Shinjuku-ku, Tokyo, Japan, 160-8582
      • Keio University Hospital /ID# 237210
  • Yamanashi
    • Kai-shi, Yamanashi, Japan, 400-0124
      • Nagaseki Headache Clinic /ID# 234561
• Korea, Republic of
  • Busan, Korea, Republic of, 49241
    • Pusan National University Hospital /ID# 237120
  • Seoul, Korea, Republic of, 01830
    • Nowon Eulji Medical Center, Eulji University /ID# 236306
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital /ID# 237786
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center /ID# 237785
  • Gyeonggido
    • Hwaseong, Gyeonggido, Korea, Republic of, 18450
      • Dongtan Sacred Heart Hospital /ID# 238097
  • Seoul Teugbyeolsi
    • Seoul, Seoul Teugbyeolsi, Korea, Republic of, 03181
      • Kangbuk Samsung Hospital /ID# 237754
    • Seoul, Seoul Teugbyeolsi, Korea, Republic of, 03722
      • Yonsei University Health System Severance Hospital /ID# 237839
• Poland
  • Kujawsko-pomorskie
    • Bydgoszcz, Kujawsko-pomorskie, Poland, 85-079
      • NZOZ Vitamed /ID# 237041
  • Lubelskie
    • Lublin, Lubelskie, Poland, 20-582
      • Indywidualna Praktyka Lekarska dr hab. med. Anna Szczepanska-Szerej /ID# 236289
  • Malopolskie
    • Krakow, Malopolskie, Poland, 30-539
      • Specjalistyczne Gabinety Sp. z o.o. /ID# 236348
    • Krakow, Malopolskie, Poland, 31-209
      • Centrum Leczenia Padaczki i Migreny /ID# 236386
  • Pomorskie
    • Gdynia, Pomorskie, Poland, 81-338
      • Centrum Medyczne Pratia Gdynia /ID# 237077
  • Slaskie
    • Katowice, Slaskie, Poland, 40-282
      • Silmedic Sp. z o.o. /ID# 237343
  • Wielkopolskie
    • Poznan, Wielkopolskie, Poland, 60-529
      • Solumed Centrum Medyczne /ID# 236452
  • Zachodniopomorskie
    • Szczecin, Zachodniopomorskie, Poland, 70-111
      • EuroMedis sp. z o.o. /ID# 236417
• Russian Federation
  • Moscow, Russian Federation, 119221
    • University Headache Clinic /ID# 236371
  • Moscow, Russian Federation, 125047
    • Clinics Chaika /ID# 236394
  • Moscow, Russian Federation, 129128
    • Central Clinical Hospital RZHD Medicine /ID# 237024
  • Tatarstan, Respublika
    • Kazan, Tatarstan, Respublika, Russian Federation, 420012
      • Kazan State Medical University /ID# 236298
    • Kazan, Tatarstan, Respublika, Russian Federation, 420021
      • State Autonomous Healthcare Institution Republican Clinical Neurology Centre /ID# 236354
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall d'Hebron /ID# 236467
  • Sevilla, Spain, 41013
    • Hospital Universitario Virgen del Rocio /ID# 237106
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario de Valencia /ID# 237400
  • Valencia, Spain, 46026
    • Hospital Universitario y Politecnico La Fe /ID# 237087
  • Valladolid, Spain, 47003
    • Hospital Clinico Universitario de Valladolid /ID# 234406
  • Zaragoza, Spain, 50009
    • Hospital Clinico Universitario Lozano Blesa /ID# 237373
  • A Coruna
    • Santiago de Compostela, A Coruna, Spain, 15706
      • Hospital Clínico Universitario de Santiago-CHUS /ID# 237623
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • CLINICA UNIVERSIDAD DE NAVARRA-Pamplona /ID# 237645
• Sweden
  • Helsingborg, Sweden, 252 20
    • Stortorgets Neurologmottagning /ID# 236454
• Taiwan
  • Taichung City, Taiwan, 433
    • Kuang-Tien General Hospital /ID# 236309
  • Tainan, Taiwan, 71004
    • Chi-Mei Medical Center /ID# 236724
  • Tainan City, Taiwan, 70142
    • Tainan Sin Lau Hospital /ID# 236358
  • Taipei City, Taiwan, 11217
    • Taipei Veterans General Hosp /ID# 237236
  • Taipei City, Taiwan, 11490
    • Tri-Service General Hospital /ID# 237657
• United Kingdom
  • Liverpool, United Kingdom, L9 7LJ
    • Walton Centre /ID# 236468
  • London, United Kingdom, SE5 9RS
    • King's College Hospital NHS Foundation Trust /ID# 236301
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • Barrow Neuro Institute /ID# 236776
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Baptist Health Center for Clinical Research /ID# 237361
  • California
    • Fresno, California, United States, 93720
      • California Headache and Balance Center /ID# 236246
    • Los Alamitos, California, United States, 90720
      • Wr-Pri Llc /Id# 236008
    • Newport Beach, California, United States, 92660
      • Pharmacology Research Institute (PRI) - Newport Beach (Wake) /ID# 237692
    • Sherman Oaks, California, United States, 91403
      • Schuster Medical Research Institute /ID# 236447
  • Colorado
    • Boulder, Colorado, United States, 80301-1880
      • Alpine Clinical Research Center /ID# 234346
  • District of Columbia
    • Washington, District of Columbia, United States, 20037-3201
      • George Washington University Medical Faculty Associates /ID# 238011
  • Florida
    • Saint Petersburg, Florida, United States, 33709-3113
      • Accel Research Sites - St Petersburg Clinical Research Unit /ID# 237161
    • Tampa, Florida, United States, 33634
      • Accel Research Sites - Tampa Clinical Research Unit /ID# 237485
    • West Palm Beach, Florida, United States, 33407-3209
      • Premiere Research Institute - Palm Beach /ID# 238192
  • Georgia
    • Atlanta, Georgia, United States, 30328
      • NeuroTrials Research Inc. /ID# 237364
  • Indiana
    • Indianapolis, Indiana, United States, 46256-4692
      • Josephson-Wallack-Munshower Neurology - NE /ID# 238234
  • Kansas
    • Prairie Village, Kansas, United States, 66208
      • Collective Medical Research /ID# 236400
  • Louisiana
    • Covington, Louisiana, United States, 70433-8107
      • Ochsner Clinic Foundation /ID# 236543
  • Massachusetts
    • Boston, Massachusetts, United States, 02215-5400
      • Beth Israel Deaconess Medical Center /ID# 237540
    • New Bedford, Massachusetts, United States, 02740
      • BTC of New Bedford /ID# 236384
  • Minnesota
    • Minneapolis, Minnesota, United States, 55402-2606
      • Clinical Research Institute, Inc /ID# 238299
  • Mississippi
    • Ridgeland, Mississippi, United States, 39157
      • Headache Neurology Research Institute /ID# 236464
  • Nevada
    • Las Vegas, Nevada, United States, 89113
      • Nevada Headache Institute /ID# 236420
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth-Hitchcock Medical Center /ID# 237444
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • Albuquerque Clinical Trials, Inc /ID# 236853
  • New York
    • Albany, New York, United States, 12208-3412
      • Albany Medical Center Rheumatology /ID# 236540
    • Amherst, New York, United States, 14226
      • Dent Neurosciences Research Center, Inc. /ID# 237040
  • North Carolina
    • Greensboro, North Carolina, United States, 27405
      • Headache Wellness Center /ID# 236431
    • Raleigh, North Carolina, United States, 27607
      • Raleigh Neurology Associates /ID# 237141
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Stetson-University of Cincinnati /ID# 236453
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19001
      • Abington Neurological Associates - Abington /ID# 236258
    • Pittsburgh, Pennsylvania, United States, 15236
      • Preferred Primary Care Physicians, Inc. /ID# 236439
  • Tennessee
    • Chattanooga, Tennessee, United States, 37421-1605
      • WR-ClinSearch /ID# 238288
    • Memphis, Tennessee, United States, 38119
      • Clinical Neuroscience Solutions - Memphis /ID# 237478
  • Texas
    • Bryan, Texas, United States, 77802
      • DiscoveResearch, Inc /ID# 236274
    • Dallas, Texas, United States, 75214
      • Texas Neurology /ID# 236359
    • Dallas, Texas, United States, 75390-7208
      • University of Texas Southwestern Medical Center /ID# 236941
  • Utah
    • Salt Lake City, Utah, United States, 84109
      • J. Lewis Research, Inc. / Foothill Family Clinic /ID# 236395
    • Salt Lake City, Utah, United States, 84121
      • J. Lewis Research, Inc. Foothill Family Clinic South /ID# 236297
    • Salt Lake City, Utah, United States, 84124
      • Highland Clinical Research /ID# 237816
  • Virginia
    • McLean, Virginia, United States, 22101
      • MedStar Georgetown Neurology /ID# 236324
    • Virginia Beach, Virginia, United States, 23456-0019
      • Sentara Neurology Specialists - Virginia Beach /ID# 234349
  • Washington
    • Bellevue, Washington, United States, 98007
      • Northwest Clinical Research Center /ID# 237581
    • Tacoma, Washington, United States, 25328
      • Puget Sound Neurology /ID# 236321

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• At least a 1-year history of chronic migraine (CM) consistent with a diagnosis according to the International Classification of Headache Disorders, 3rd Edition (ICHD-3), 2018
• Age of the participant at the time of migraine onset < 50 years

• Confirmation of headache/migraine headache day frequency as follows:

  • History of, on average, ≥ 15 headache days per month in the 3 months prior to Visit 1 in the opinion of the investigator AND
  • >=15 headache days during the 4-week screening/baseline period per the electronic diary (eDiary) AND
  • >=8 days during the 4-week screening/baseline period that qualify as being a migraine day per the eDiary
• Participants must be using a medically acceptable and effective method of birth control during the course of the entire study

Exclusion Criteria:

• Has a history of migraine, accompanied by diplopia or decreased level of consciousness, or retinal migraine
• Has a current diagnosis of new persistent daily headache, trigeminal autonomic cephalgia (eg, cluster headache), or painful cranial neuropathy
• History of an inadequate response to > 4 medications (2 of which have different mechanisms of action) prescribed for the prevention of migraine
• Woman is pregnant, planning to become pregnant during the course of the study, or currently lactating. Women of childbearing potential must have a negative urine pregnancy test at Visit 1 and Visit 2.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Participants received atogepant-matching placebo tablets, orally, twice daily (BID) for 12 weeks in a double-blind (DB) treatment period.	Drug: Placebo; 30 mg/60 mg tablets containing atogepant-matching placebo
Active Comparator: Atogepant 30 mg BID; Participants received atogepant 30 mg tablet, orally, BID and atogepant-matching placebo tablets orally, BID for up to 12 weeks in a DB treatment period.	Drug: Atogepant 30 mg; Tablets containing 30 mg atogepant; Drug: Placebo; 30 mg/60 mg tablets containing atogepant-matching placebo
Active Comparator: Atogepant 60 mg QD; Participants received atogepant 60 mg, orally, once daily (QD) along with atogepant-matching placebo 30 mg as morning dose followed by atogepant-matching placebo 30 mg and 60 mg as evening doses for up to 12 weeks in a DB treatment period.	Drug: Atogepant 60 mg; Tablets containing 60 mg atogepant; Drug: Placebo; 30 mg/60 mg tablets containing atogepant-matching placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Mean Monthly Migraine Days Across 12-Week Treatment Period in mITT Population	Participants recorded daily duration of migraine in a diary. A migraine day was any calendar day on which the participant experienced a migraine headache. The monthly (4-week) migraine days were defined as the total number of reported migraine days in diary divided by total number of days with diary records during each 4-week period and multiplied by 28. Each 4-week period was averaged. Baseline is defined as the number of migraine days during the last 28 days prior to the randomization date. Negative change from Baseline indicates improvement. A contrast from Mixed-effects model for repeated measures (MMRM) was used to obtain the average treatment effects across the 12-week treatment period.	Baseline to Week 12
Change From Baseline in Mean Monthly Migraine Days Across 12-Week Treatment Period in Off-Treatment Hypothetical Estimand Population	Participants recorded daily duration of migraine in a diary. A migraine day was any calendar day on which the participant experienced a migraine headache. The monthly (4-week) migraine days were defined as the total number of reported migraine days in diary divided by total number of days with diary records during each 4-week period and multiplied by 28. Each 4-week period was averaged. Baseline is defined as the number of migraine days during the last 28 days prior to the randomization date. Negative change from Baseline indicates improvement. A contrast from Mixed-effects model for repeated measures (MMRM) was used to obtain the average treatment effects across the 12-week treatment period.	Baseline to Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Mean Monthly Headache Days Across 12-Week Treatment Period in mITT Population	Participants recorded daily total duration of a headache in a diary. A headache day is any calendar day on which the participant experienced a headache pain lasting 2 hours or longer unless an acute headache medication was used after the start of the headache. The monthly (4-week) headache days were defined as the total number of reported headache days in the diary divided by the total number of days with diary records during each 4-week period and multiplied by 28. Each 4-week period was averaged. Baseline is defined as the number of headache days during the last 28 days prior to the randomization date. Negative change from Baseline indicates improvement. A contrast from MMRM was used to obtain the average treatment effects across the 12-week treatment period.	Baseline to Week 12
Change From Baseline in Mean Monthly Headache Days Across 12-Week Treatment Period in Off-Treatment Hypothetical Estimand Population	Participants recorded daily total duration of a headache in a diary. A headache day is any calendar day on which the participant experienced a headache pain lasting 2 hours or longer unless an acute headache medication was used after the start of the headache. The monthly (4-week) headache days were defined as the total number of reported headache days in the diary divided by the total number of days with diary records during each 4-week period and multiplied by 28. Each 4-week period was averaged. Baseline is defined as the number of headache days during the last 28 days prior to the randomization date. Negative change from Baseline indicates improvement. A contrast from MMRM was used to obtain the average treatment effects across the 12-week treatment period.	Baseline to Week 12
Change From Baseline in Mean Monthly Acute Medication Use Days Across 12-Week Treatment Period in mITT Population	An acute medication use day is defined as any day on which a participant reports, per eDiary, the intake of allowed medication(s) to treat an acute migraine. The monthly (4-week) acute medication use days were defined as the total number of reported acute medication use days in the diary divided by the total number of days with diary records during each 4-week period and multiplied by 28. Each 4-week period was averaged. Baseline is defined as the number of migraine days during the last 28 days prior to the randomization date. A negative change from Baseline indicates improvement. A contrast from MMRM was used to obtain the average treatment effects across the 12-week treatment period.	Baseline to Week 12
Change From Baseline in Mean Monthly Acute Medication Use Days Across 12-Week Treatment Period in Off-treatment Hypothetical Estimand Population	An acute medication use day is defined as any day on which a participant reports, per eDiary, the intake of allowed medication(s) to treat an acute migraine. The monthly (4-week) acute medication use days were defined as the total number of reported acute medication use days in the diary divided by the total number of days with diary records during each 4-week period and multiplied by 28. Each 4-week period was averaged. Baseline is defined as the number of migraine days during the last 28 days prior to the randomization date. A negative change from Baseline indicates improvement. A contrast from MMRM was used to obtain the average treatment effects across the 12-week treatment period.	Baseline to Week 12
Percentage of Participants With at Least a 50% Reduction in 3-Month Average of Monthly Migraine Days in mITT Population	Data is reported for 50% responders averaged at each 4-week period. 50% responders are participants with at least a 50 percent reduction from baseline in 3-month average of monthly migraine days. Participants recorded daily duration of migraine in a diary. A migraine day was any calendar day on which the participant experienced a migraine headache. The monthly (4-week) migraine days is equal to total number of reported migraine days in diary divided by total number of days with diary records in each 4-week period multiplied by 28. The values are rounded off to the first decimal value.	Baseline to Week 12
Percentage of Participants With at Least a 50% Reduction in 3-Month Average of Monthly Migraine Days in Off-Treatment Hypothetical Estimand Population	Data is reported for 50% responders averaged at each 4-week period. 50% responders are participants with at least a 50 percent reduction from baseline in 3-month average of monthly migraine days. Participants recorded daily duration of migraine in a diary. A migraine day was any calendar day on which the participant experienced a migraine headache. The monthly (4-week) migraine days is equal to total number of reported migraine days in diary divided by total number of days with diary records in each 4-week period multiplied by 28. The values are rounded off to the first decimal value.	Baseline to Week 12
Change From Baseline in Migraine Specific Quality of Life Questionnaire, Version 2.1 (MSQ v2.1) Role Function-Restrictive Domain Score at Week 12 in Off-Treatment Hypothetical Estimand Population	The 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 3 domains: Role Function Restrictive (question numbers 1-7, score ranges 7 to 42) assesses how migraines limit one's daily social and work-related activities; Role Function Preventive (question numbers 8-11, score ranges 4 to 24) assesses how migraines prevent these activities; and the Emotional Function (question numbers 12-14, score ranges 3 to 18) domain assesses the emotions associated with migraines. 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. A contrast from MMRM was used to obtain the average treatment effects across the 12-week treatment period.	At Week 12
Change From Baseline in Mean Monthly Performance of Daily Activities Domain Score of the AIM-D Across 12-Week Treatment Period in mITT Population	The AIM-D is a 11-item patient-reported outcome (PRO) measure that assesses the impact of migraine on the performance of daily activities which include, 7 items: difficulty with household chores, errands, leisure activities at home, leisure or social activities outside the home, strenuous physical activities, concentrating, and thinking clearly and physical impairment; 4 items: difficulty walking, moving body, bending forward, moving head using a 6-point rating scale where 0=not difficult at all, 1=a little difficult, 2=somewhat difficult, 3=very difficult, 4=extremely difficult, and 5=I could not do it at all. The raw performance of daily activities domain scores were transformed to 0-100 scale, with higher scores indicating greater impact of migraine (higher disease burden). A contrast from MMRM was used to obtain the average treatment effects across the 12-week treatment period.	Baseline to Week 12
Change From Baseline in Mean Monthly Physical Impairment Domain Score of the AIM-D Across 12-Week Treatment Period in mITT Population	The AIM-D is a 11-item PRO measure that assesses the impact of migraine on the performance of daily activities which includes 7 items: difficulty with household chores, errands, leisure activities at home, leisure or social activities outside the home, strenuous physical activities, concentrating, and thinking clearly and physical impairment; 4 items: difficulty walking, moving body, bending forward, moving head using a 6-point rating scale where 0=not difficult at all, 1=a little difficult, 2=somewhat difficult, 3=very difficult, 4=extremely difficult, and 5=I could not do it at all. The raw physical impairment domain scores were transformed to 0-100 scale, with higher scores indicating greater impact of migraine (higher disease burden). A contrast from MMRM was used to obtain the average treatment effects across the 12-week treatment period.	Baseline to Week 12
Change From Baseline in the Headache Impact Test (HIT-6) Total Score at Week 12 in Off-Treatment Hypothetical Estimand Population	HIT-6 is a 6-question assessment used to measure the impact headaches have on a participant's ability to function on the job, at school, at home, and in social situations. It assesses the effect that headaches have on normal daily life and the participant's ability to function. 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). MMRM was used for the analyses.	At Week 12

Collaborators and Investigators

• Sponsor: Allergan

Publications and helpful links

General Publications

• Boinpally R, McNamee B, Yao L, Butler M, McGeeney D, Borbridge L, Periclou A. A Single Supratherapeutic Dose of Atogepant Does Not Affect Cardiac Repolarization in Healthy Adults: Results From a Randomized, Single-Dose, Phase 1 Crossover Trial. Clin Pharmacol Drug Dev. 2021 Sep;10(9):1099-1107. doi: 10.1002/cpdd.940. Epub 2021 May 4.
• Min KC, Kraft WK, Bondiskey P, Colon-Gonzalez F, Liu W, Xu J, Panebianco D, Mixson L, Dockendorf MF, Matthews CZ, Boinpally R. Atogepant Is Not Associated With Clinically Meaningful Alanine Aminotransferase Elevations in Healthy Adults. Clin Transl Sci. 2021 Mar;14(2):599-605. doi: 10.1111/cts.12917. Epub 2020 Nov 24.

Helpful Links

• Related Information

Study record dates

Study Major Dates

• Study Start (Actual): March 11, 2019
• Primary Completion (Actual): January 20, 2022
• Study Completion (Actual): January 20, 2022

Study Registration Dates

• First Submitted: February 25, 2019
• First Submitted That Met QC Criteria: February 25, 2019
• First Posted (Actual): February 26, 2019

Study Record Updates

• Last Update Posted (Actual): February 14, 2023
• Last Update Submitted That Met QC Criteria: January 18, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders
• Other Study ID Numbers: 3101-303-002; 2018-004337-32 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols, analyses plans, clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
• IPD Sharing Time Frame: For details on when studies are available for sharing visit, please refer to the link below.
• IPD Sharing Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Use Agreement (DUA). For more information on the process, or to submit a request, visit the following link.
• 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