Clinical trial NCT03855137: Efficacy, Safety, and Tolerability of Atogepant for the Prevention of Chronic Migraine
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Migraine
Lead sponsor: Allergan
Sponsor class: INDUSTRY
First posted: 2019-02-26
Enrollment: 778
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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.

Primary outcomes:
measure: Change From Baseline in Mean Monthly Migraine Days Across 12-Week Treatment Period in mITT Population
timeFrame: Baseline to Week 12
measure: Change From Baseline in Mean Monthly Migraine Days Across 12-Week Treatment Period in Off-Treatment Hypothetical Estimand Population
timeFrame: Baseline to Week 12
Secondary outcomes:
measure: Change From Baseline in Mean Monthly Headache Days Across 12-Week Treatment Period in mITT Population
timeFrame: Baseline to Week 12
measure: Change From Baseline in Mean Monthly Headache Days Across 12-Week Treatment Period in Off-Treatment Hypothetical Estimand Population
timeFrame: Baseline to Week 12
measure: Change From Baseline in Mean Monthly Acute Medication Use Days Across 12-Week Treatment Period in mITT Population
timeFrame: Baseline to Week 12
measure: Change From Baseline in Mean Monthly Acute Medication Use Days Across 12-Week Treatment Period in Off-treatment Hypothetical Estimand Population
timeFrame: Baseline to Week 12
measure: Percentage of Participants With at Least a 50% Reduction in 3-Month Average of Monthly Migraine Days in mITT Population
timeFrame: Baseline to Week 12
measure: Percentage of Participants With at Least a 50% Reduction in 3-Month Average of Monthly Migraine Days in Off-Treatment Hypothetical Estimand Population
timeFrame: Baseline to Week 12
measure: 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
timeFrame: At Week 12
measure: Change From Baseline in Mean Monthly Performance of Daily Activities Domain Score of the AIM-D Across 12-Week Treatment Period in mITT Population
timeFrame: Baseline to Week 12
measure: Change From Baseline in Mean Monthly Physical Impairment Domain Score of the AIM-D Across 12-Week Treatment Period in mITT Population
timeFrame: Baseline to Week 12
measure: Change From Baseline in the Headache Impact Test (HIT-6) Total Score at Week 12 in Off-Treatment Hypothetical Estimand Population
timeFrame: At Week 12
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Barrow Neuro Institute /ID# 236776
state: Arizona
city: Little Rock
country: United States
facility: Baptist Health Center for Clinical Research /ID# 237361
state: Arkansas
city: Fresno
country: United States
facility: California Headache and Balance Center /ID# 236246
state: California
city: Los Alamitos
country: United States
facility: Wr-Pri Llc /Id# 236008
state: California
city: Newport Beach
country: United States
facility: Pharmacology Research Institute (PRI) - Newport Beach (Wake) /ID# 237692
state: California
city: Sherman Oaks
country: United States
facility: Schuster Medical Research Institute /ID# 236447
state: California
city: Boulder
country: United States
facility: Alpine Clinical Research Center /ID# 234346
state: Colorado
city: Washington
country: United States
facility: George Washington University Medical Faculty Associates /ID# 238011
state: District of Columbia
city: Saint Petersburg
country: United States
facility: Accel Research Sites - St Petersburg Clinical Research Unit /ID# 237161
state: Florida
city: Tampa
country: United States
facility: Accel Research Sites - Tampa Clinical Research Unit /ID# 237485
state: Florida
city: West Palm Beach
country: United States
facility: Premiere Research Institute - Palm Beach /ID# 238192
state: Florida
city: Atlanta
country: United States
facility: NeuroTrials Research Inc. /ID# 237364
state: Georgia
city: Indianapolis
country: United States
facility: Josephson-Wallack-Munshower Neurology - NE /ID# 238234
state: Indiana
city: Prairie Village
country: United States
facility: Collective Medical Research /ID# 236400
state: Kansas
city: Covington
country: United States
facility: Ochsner Clinic Foundation /ID# 236543
state: Louisiana
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center /ID# 237540
state: Massachusetts
city: New Bedford
country: United States
facility: BTC of New Bedford /ID# 236384
state: Massachusetts
city: Minneapolis
country: United States
facility: Clinical Research Institute, Inc /ID# 238299
state: Minnesota
city: Ridgeland
country: United States
facility: Headache Neurology Research Institute /ID# 236464
state: Mississippi
city: Las Vegas
country: United States
facility: Nevada Headache Institute /ID# 236420
state: Nevada
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center /ID# 237444
state: New Hampshire
city: Albuquerque
country: United States
facility: Albuquerque Clinical Trials, Inc /ID# 236853
state: New Mexico
city: Albany
country: United States
facility: Albany Medical Center Rheumatology /ID# 236540
state: New York
city: Amherst
country: United States
facility: Dent Neurosciences Research Center, Inc. /ID# 237040
state: New York
city: Greensboro
country: United States
facility: Headache Wellness Center /ID# 236431
state: North Carolina
city: Raleigh
country: United States
facility: Raleigh Neurology Associates /ID# 237141
state: North Carolina
city: Cincinnati
country: United States
facility: Stetson-University of Cincinnati /ID# 236453
state: Ohio
city: Abington
country: United States
facility: Abington Neurological Associates - Abington /ID# 236258
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Preferred Primary Care Physicians, Inc. /ID# 236439
state: Pennsylvania
city: Chattanooga
country: United States
facility: WR-ClinSearch /ID# 238288
state: Tennessee
city: Memphis
country: United States
facility: Clinical Neuroscience Solutions - Memphis /ID# 237478
state: Tennessee
city: Bryan
country: United States
facility: DiscoveResearch, Inc /ID# 236274
state: Texas
city: Dallas
country: United States
facility: Texas Neurology /ID# 236359
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center /ID# 236941
state: Texas
city: Salt Lake City
country: United States
facility: J. Lewis Research, Inc. / Foothill Family Clinic /ID# 236395
state: Utah
city: Salt Lake City
country: United States
facility: J. Lewis Research, Inc. Foothill Family Clinic South /ID# 236297
state: Utah
city: Salt Lake City
country: United States
facility: Highland Clinical Research /ID# 237816
state: Utah
city: McLean
country: United States
facility: MedStar Georgetown Neurology /ID# 236324
state: Virginia
city: Virginia Beach
country: United States
facility: Sentara Neurology Specialists - Virginia Beach /ID# 234349
state: Virginia
city: Bellevue
country: United States
facility: Northwest Clinical Research Center /ID# 237581
state: Washington
city: Tacoma
country: United States
facility: Puget Sound Neurology /ID# 236321
state: Washington
city: St Leonards
country: Australia
facility: Royal North Shore Hospital /ID# 237008
state: New South Wales
city: Parkville
country: Australia
facility: The Royal Melbourne Hospital /ID# 236859
state: Victoria
city: Calgary
country: Canada
facility: CHAMP Clinic /ID# 236252
state: Alberta
city: Victoria
country: Canada
facility: Vancouver Island Health Authority /ID# 238053
state: British Columbia
city: Ottawa
country: Canada
facility: Ottawa Headache Centre Research Inc /ID# 236432
state: Ontario
city: Montreal
country: Canada
facility: Clinique des cephalees de Montreal /ID# 236266
state: Quebec
city: Montreal
country: Canada
facility: Montreal Neurological Institut /ID# 236329
state: Quebec
city: Beijing
country: China
facility: Peking University Third Hospital /ID# 238150
state: Beijing
city: Beijing
country: China
facility: Chinese PLA General Hospital /ID# 238237
state: Beijing
city: Guangzhou
country: China
facility: Guangzhou First People's Hospital /ID# 236510
state: Guangdong
city: Guangzhou
country: China
facility: The Second Affiliated Hospital of Guangzhou Medical University /ID# 238133
state: Guangdong
city: Wuhan
country: China
facility: Hubei General Hospital /ID# 236486
state: Hebei
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University /ID# 237025
state: Henan
city: Nanjing
country: China
facility: Jiangsu Province Hospital /ID# 237846
state: Jiangsu
city: Changchun
country: China
facility: The Second Hospital of Jilin University /ID# 236520
state: Jilin
city: Shanghai
country: China
facility: Ruijin Hospital, Shanghai Jiaotong University School of Medicine /ID# 237847
state: Shanghai
city: Taiyuan
country: China
facility: The Second Hospital of Shanxi Medical University /ID# 236529
state: Shanxi
city: Hangzhou
country: China
facility: The second Affiliated hospital of Zhejiang University school of Medicine /ID# 238260
state: Zhejiang
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital Zhejiang University School of Medicine /ID# 236500
state: Zhejiang
city: Beijing
country: China
facility: Beijing Friendship Hospital /ID# 237264
city: Suzhou
country: China
facility: The Second Hospital of Soochow University /ID# 234296
city: Tianjin
country: China
facility: Tianjin Huanhu Hospital (THH) /ID# 236524
city: Wuhan
country: China
facility: Tongji Hospital Tongji Medical College of HUST /ID# 237835
city: Hradec Kralove
country: Czechia
facility: NEUROHK s.r.o. /ID# 236290
city: Kladno
country: Czechia
facility: BRAIN-SOULTHERAPY s.r.o. /ID# 236380
city: Ostrava
country: Czechia
facility: CCR Ostrava, s.r.o. /ID# 234291
city: Prague 10
country: Czechia
facility: CLINTRIAL s.r.o. /ID# 237793
city: Prague 4
country: Czechia
facility: CCR Czech a.s /ID# 236249
city: Prague
country: Czechia
facility: FORBELI s.r.o. /ID# 236427
city: Praha
country: Czechia
facility: CCR Prague s.r.o. /ID# 236250
city: Praha
country: Czechia
facility: Thomayerova nemocnice /ID# 237175
city: Zlin
country: Czechia
facility: NeuroMed Zlin s.r.o. /ID# 236416
city: Glostrup
country: Denmark
facility: Rigshospitalet Glostrup /ID# 236411
state: Hovedstaden
city: Marseille CEDEX 05
country: France
facility: AP-HM - Hopital de la Timone /ID# 236285
state: Bouches-du-Rhone
city: PRINGY cedex
country: France
facility: CH Annecy Genevois Site Annecy /ID# 236385
state: Haute-Savoie
city: Bron
country: France
facility: Hôpital Pierre Wertheimer /ID# 236969
city: Clermont Ferrand
country: France
facility: CHU Gabriel Montpied /ID# 237323
city: Berlin
country: Germany
facility: Charite Universitaetsklinikum Berlin - Campus Virchow /ID# 237256
city: Essen
country: Germany
facility: Praxis Dr. Gendolla /ID# 236311
city: Essen
country: Germany
facility: Universitaetsklinikum Essen /ID# 237209
city: Hamburg
country: Germany
facility: CTC North GmbH & Co. KG /ID# 236328
city: Kassel
country: Germany
facility: Vitos Orthopaedische Klinik Kassel gemeinnuetzige GmbH /ID# 236723
city: Kiel
country: Germany
facility: Schmerzklinik Kiel /ID# 236444
city: München
country: Germany
facility: LMU Klinikum Campus Grosshadern /ID# 236293
city: Bari
country: Italy
facility: Azienda Ospedaliera Universitaria Consorziale Policlinico /ID# 237492
city: Florence
country: Italy
facility: Azienda Ospedaliero Universitaria Careggi /ID# 237598
city: Milan
country: Italy
facility: Fondazione IRCCS Istituto Neurologico Carlo Besta /ID# 237291
city: Napoli
country: Italy
facility: AOU Universita degli Studi della Campania Luigi Vanvitelli /ID# 236361
city: Pavia
country: Italy
facility: Universita di Pavia /ID# 236363
city: Rome
country: Italy
facility: IRCCS San Raffaele Pisana /ID# 236552
city: Matsuyama-shi
country: Japan
facility: Takanoko Hospital /ID# 234564
state: Ehime
city: Fukui-shi
country: Japan
facility: Fukuiken Saiseikai Hospital /ID# 236794
state: Fukui
city: Sapporo-shi
country: Japan
facility: Higashi Sapporo Neurology and Neurosurgery Clinic /ID# 234549
state: Hokkaido
city: Kobe-shi
country: Japan
facility: Konan Medical Center /ID# 236230
state: Hyogo
city: Kagoshima-shi
country: Japan
facility: Atsuchi Neurosurgical Hospital /ID# 234779
state: Kagoshima
city: Isehara-shi
country: Japan
facility: Tokai University Hospital /ID# 237595
state: Kanagawa
city: Kawasaki-shi
country: Japan
facility: Fujitsu Clinic /ID# 237443
state: Kanagawa
city: Kochi-shi
country: Japan
facility: Umenotsuji Clinic /ID# 234495
state: Kochi
city: Sendai-shi
country: Japan
facility: Sendai Headache and Neurology Clinic Medical Corporation /ID# 234496
state: Miyagi
city: Iruma-gun
country: Japan
facility: Saitama Medical University Hospital /ID# 237019
state: Saitama
city: Saitama-shi
country: Japan
facility: Saitama Neuropsychiatric Institute /Id# 234550
state: Saitama
city: Shizuoka-shi
country: Japan
facility: Japanese Red Cross Shizuoka Hospital /ID# 234372
state: Shizuoka
city: Shimotsuga-gun
country: Japan
facility: Dokkyo Medical University Hospital /ID# 236810
state: Tochigi
city: Chofu-shi
country: Japan
facility: Niwa Family Clinic /ID# 234552
state: Tokyo
city: Shibuya-ku
country: Japan
facility: Tokyo Headache Clinic /ID# 234555
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Keio University Hospital /ID# 237210
state: Tokyo
city: Kai-shi
country: Japan
facility: Nagaseki Headache Clinic /ID# 234561
state: Yamanashi
city: Hiroshima
country: Japan
facility: DOI Internal Medicine-Neurology Clinic /ID# 234562
city: Hiroshima
country: Japan
facility: Hiroshima Neurology Clinic /ID# 234563
city: Kagoshima
country: Japan
facility: Tanaka Neurosurgical clinic /ID# 234760
city: Kyoto
country: Japan
facility: Tatsuoka Neurology Clinic /ID# 234782
city: Osaka
country: Japan
facility: Tominaga Hospital /ID# 234781
city: Tokyo
country: Japan
facility: Shinagawa Strings Clinic /ID# 234780
city: Hwaseong
country: Korea, Republic of
facility: Dongtan Sacred Heart Hospital /ID# 238097
state: Gyeonggido
city: Seoul
country: Korea, Republic of
facility: Kangbuk Samsung Hospital /ID# 237754
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Yonsei University Health System Severance Hospital /ID# 237839
state: Seoul Teugbyeolsi
city: Busan
country: Korea, Republic of
facility: Pusan National University Hospital /ID# 237120
city: Seoul
country: Korea, Republic of
facility: Nowon Eulji Medical Center, Eulji University /ID# 236306
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital /ID# 237786
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center /ID# 237785
city: Bydgoszcz
country: Poland
facility: NZOZ Vitamed /ID# 237041
state: Kujawsko-pomorskie
city: Lublin
country: Poland
facility: Indywidualna Praktyka Lekarska dr hab. med. Anna Szczepanska-Szerej /ID# 236289
state: Lubelskie
city: Krakow
country: Poland
facility: Specjalistyczne Gabinety Sp. z o.o. /ID# 236348
state: Malopolskie
city: Krakow
country: Poland
facility: Centrum Leczenia Padaczki i Migreny /ID# 236386
state: Malopolskie
city: Gdynia
country: Poland
facility: Centrum Medyczne Pratia Gdynia /ID# 237077
state: Pomorskie
city: Katowice
country: Poland
facility: Silmedic Sp. z o.o. /ID# 237343
state: Slaskie
city: Poznan
country: Poland
facility: Solumed Centrum Medyczne /ID# 236452
state: Wielkopolskie
city: Szczecin
country: Poland
facility: EuroMedis sp. z o.o. /ID# 236417
state: Zachodniopomorskie
city: Kazan
country: Russian Federation
facility: Kazan State Medical University /ID# 236298
state: Tatarstan, Respublika
city: Kazan
country: Russian Federation
facility: State Autonomous Healthcare Institution Republican Clinical Neurology Centre /ID# 236354
state: Tatarstan, Respublika
city: Moscow
country: Russian Federation
facility: University Headache Clinic /ID# 236371
city: Moscow
country: Russian Federation
facility: Clinics Chaika /ID# 236394
city: Moscow
country: Russian Federation
facility: Central Clinical Hospital RZHD Medicine /ID# 237024
city: Santiago de Compostela
country: Spain
facility: Hospital Clínico Universitario de Santiago-CHUS /ID# 237623
state: A Coruna
city: Pamplona
country: Spain
facility: CLINICA UNIVERSIDAD DE NAVARRA-Pamplona /ID# 237645
state: Navarra
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron /ID# 236467
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio /ID# 237106
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia /ID# 237400
city: Valencia
country: Spain
facility: Hospital Universitario y Politecnico La Fe /ID# 237087
city: Valladolid
country: Spain
facility: Hospital Clinico Universitario de Valladolid /ID# 234406
city: Zaragoza
country: Spain
facility: Hospital Clinico Universitario Lozano Blesa /ID# 237373
city: Helsingborg
country: Sweden
facility: Stortorgets Neurologmottagning /ID# 236454
city: Taichung City
country: Taiwan
facility: Kuang-Tien General Hospital /ID# 236309
city: Tainan City
country: Taiwan
facility: Tainan Sin Lau Hospital /ID# 236358
city: Tainan
country: Taiwan
facility: Chi-Mei Medical Center /ID# 236724
city: Taipei City
country: Taiwan
facility: Taipei Veterans General Hosp /ID# 237236
city: Taipei City
country: Taiwan
facility: Tri-Service General Hospital /ID# 237657
city: Liverpool
country: United Kingdom
facility: Walton Centre /ID# 236468
city: London
country: United Kingdom
facility: King's College Hospital NHS Foundation Trust /ID# 236301
Study officials:
affiliation: Allergan
name: ALLERGAN INC.
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.