Atogepant for Prophylaxis of Migraine in Participants Who Failed Previous Oral Prophylactic Treatments.

Recruitment Status
COMPLETED - HAS RESULTS
(See Contacts and Locations)Verified August 2023 by Allergan
Sponsor
Allergan
Information Provided by (Responsible Party)
Allergan
Clinicaltrials.gov Identifier
NCT04740827
Other Study ID Numbers:
3101-304-002
First Submitted
February 1, 2021
First Posted
February 4, 2021
Results First Posted
August 2, 2023
Last Update Posted
September 20, 2023
Last Verified
August 2023

ClinicalTrials.gov processed this data on September 2023. Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study Description

Condition or DiseaseIntervention/Treatment
Episodic Migraine
Drug: PlaceboDrug: Atogepant 60 mg

Study Design

Study TypeInterventional
Actual Enrollment315 participants
Design AllocationRandomized
Interventional ModelParallel Assignment
MaskingDouble
Primary PurposeTreatment
Official TitleA Phase 3, Multicenter, Randomized, Double-Blind, Placebo-controlled, Parallel-Group Study to Evaluate the Efficacy, Safety, and Tolerability of Oral Atogepant for the Prophylaxis of Migraine in Participants With Episodic Migraine Who Have Previously Failed 2 to 4 Classes of Oral Prophylactic Treatments (ELEVATE)
Study Start DateMarch 4, 2021
Actual Primary Completion DateAugust 3, 2022
Actual Study Completion DateAugust 3, 2022

Groups and Cohorts

Group/CohortIntervention/Treatment
Placebo
Participants received atogepant-matching placebo tablets, orally, once daily (QD) for up to 12 weeks in a double-blind (DB) treatment period.
Drug: Placebo
Atogepant matching placebo tablets.
Atogepant 60 mg
Participants received atogepant 60 mg, orally, QD for up to 12 weeks in a DB treatment period.
Drug: Atogepant 60 mg
Atogepant tablets.

Outcome Measures

Primary Outcome Measures
  1. 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. Mixed-effects model for repeated measures (MMRM) was used for analysis.
  2. Change From Baseline in Mean Monthly Migraine Days Across 12-Week Treatment Period in OTHE 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. MMRM was used for analysis.
Secondary Outcome Measures
  1. Number of Participants With At Least a 50% Reduction in 3-Month Average of Monthly Migraine Days Across the 12-week Treatment Period in mITT Population
    Data is reported for 50% responders averaged at each 4-week period. 50% responders are participants with at least a 50% 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 are 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.
  2. Number of Participants With At Least a 50% Reduction in 3-Month Average of Monthly Migraine Days Across the 12-week Treatment Period in OTHE Population
    Data is reported for 50% responders averaged at each 4-week period. 50% responders are participants with at least a 50% 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 are 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.
  3. Change From Baseline in Mean Monthly Headache Days Across the 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. MMRM was used for analysis.
  4. Change From Baseline in Mean Monthly Headache Days Across the 12-week Treatment Period in OTHE 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. MMRM was used for analysis.
  5. Change From Baseline in Mean Monthly Acute Medication Use Days Across the 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.
  6. Change From Baseline in Mean Monthly Acute Medication Use Days Across the 12-week Treatment Period in OTHE 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.
  7. Change From Baseline in Migraine Specific Quality of Life Questionnaire (MSQ) v2.1 Role Function-Restrictive Domain Score at Week 12 in mITT 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. MMRM was used for analysis.
  8. Change From Baseline in Migraine Specific Quality of Life Questionnaire (MSQ) v2.1 Role Function-Restrictive Domain Score at Week 12 in OTHE 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. MMRM was used for analysis.
  9. Change From Baseline in Mean Monthly Performance of Daily Activities Domain Score of the Activity Impairment in Migraine - Diary (AIM-D) Across the 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).
  10. Change From Baseline in Mean Monthly Physical Impairment Domain Score of the AIM-D Across the 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).
  11. Change From Baseline in the Headache Impact Test (HIT-6) Total Score at Week 12 in OTHE 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.
  12. Number of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)
    An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study drug. TEAEs were defined as any AE with the onset that was after the first dose of study intervention.

Eligibility Criteria

Ages Eligible for Study(Adult, Older Adult)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
Inclusion Criteria
At least a 1-year history of migraine with or without aura consistent with a diagnosis according to the ICHD-3, 2018.
Age of the participant at the time of migraine onset \< 50 years -History of 4 to 14 migraine days per month on average in the 3 months prior to Visit 1 in the investigator's judgment
Female participants willing to minimize the risk of inducing pregnancy for the duration of the clinical study and follow-up period. Male participants willing to minimize the risk of inducing pregnancy for the duration of the clinical study and follow-up period.
4 to 14 migraine days in the 28-day baseline period per eDiary
Failed oral migraine prophylaxis medications from 2 to 4 medication classes
Exclusion Criteria
Any clinically significant hematologic, endocrine, pulmonary, hepatic, gastrointestinal, or neurologic disease
Participant has any other concurrent pain condition that, in the opinion of the investigator, may significantly impact the current headache disorder
In the opinion of the investigator, confounding psychiatric conditions, dementia, epilepsy, or significant neurological disorders other than migraine
Has ≥ 15 headache days per month on average across the 3 months prior to Visit 1 in the investigator's judgment
Has ≥ 15 headache days in the 28-day baseline period per eDiary
Clinically significant cardiovascular or cerebrovascular disease
Has a history of migraine accompanied by diplopia or decreased level of consciousness or retinal migraine as defined by ICHD-3, 2018
Has a current diagnosis of chronic migraine, new persistent daily headache, medication overuse headache, trigeminal autonomic cephalgia (eg, cluster headache), or painful cranial neuropathy as defined by ICHD-3, 2018

Contacts and Locations

Sponsors and CollaboratorsAllergan
Locations
Axiom Research /ID# 226379 | Colton California, United States, 92324Pharmacology Research Institute (PRI) - Encino (Wake) /ID# 226434 | Encino California, United States, 91316Pharmacology Research Institute (PRI) - Los Alamitos (Wake) /ID# 226388 | Los Alamitos California, United States, 90720-3500Pharmacology Research Institute (PRI) - Los Alamitos (Wake) /ID# 226405 | Los Alamitos California, United States, 90720-3500Excell Research, Inc /ID# 228386 | Oceanside California, United States, 92056Alpine Clinical Research Center /ID# 226201 | Boulder Colorado, United States, 80301-1880Sensible Healthcare /ID# 226197 | Ocoee Florida, United States, 34761Meridien Research /ID# 226224 | St. Petersburg Florida, United States, 33709Meridien Research /ID# 226302 | St. Petersburg Florida, United States, 33709Velocity Clinical Research - Boise /ID# 226320 | Meridian Idaho, United States, 83642Allied Physicians - Fort Wayne Neurological Center /ID# 226350 | Fort Wayne Indiana, United States, 46804Deaconess Clinic - Gateway Health Center /ID# 226481 | Newburgh Indiana, United States, 47630Pharmasite Research, Inc. /ID# 226445 | Baltimore Maryland, United States, 21208StudyMetrix Research /ID# 226297 | City of Saint Peters Missouri, United States, 63303Clinvest Research LLC /ID# 226273 | Springfield Missouri, United States, 65807Methodist Physicians Clinic /ID# 226470 | Fremont Nebraska, United States, 68025Amici Clinical Research - Raritan /ID# 226282 | Raritan New Jersey, United States, 08869Albuquerque Clinical Trials, Inc /ID# 233445 | Albuquerque New Mexico, United States, 87102CTI Clinical Trial and Consulting /ID# 226281 | Cincinnati Ohio, United States, 45212FutureSearch Trials of Neurology /ID# 226423 | Austin Texas, United States, 78731Austin Clinical Trial Partners /ID# 228387 | Austin Texas, United States, 78737DiscoveResearch, Inc /ID# 226491 | Bryan Texas, United States, 77802FutureSearch Trials of Dallas, LP /ID# 226493 | Dallas Texas, United States, 75231LinQ Research, LLC /ID# 226227 | Pearland Texas, United States, 77584Highland Clinical Research /ID# 226288 | Salt Lake City Utah, United States, 84124Northwest Clinical Research Center /ID# 226228 | Bellevue Washington, United States, 98007Alfred Health /ID# 226341 | Melbourne Victoria, Australia, 3004The Royal Melbourne Hospital /ID# 226402 | Parkville Victoria, Australia, 3050Aggarwal and Associates Limited /ID# 226321 | Brampton Ontario, Canada, L6T 0G1Ottawa Headache Centre Research Inc /ID# 226257 | Ottawa Ontario, Canada, K2G 6E2Diex Recherche Sherbrooke Inc. /ID# 226375 | Sherbrooke Quebec, Canada, J1L 0H8POLIKLINIKA CHOCEN, a.s. /ID# 226510 | Choceň , Czechia, 565 01BRAIN-SOULTHERAPY s.r.o. /ID# 226489 | Kladno , Czechia, 272 01CCR Ostrava, s.r.o. /ID# 226279 | Ostrava , Czechia, 702 00A-SHINE s.r.o. /ID# 226208 | Pilsen , Czechia, 301 00CLINTRIAL s.r.o. /ID# 226192 | Prague , Czechia, 100 00DADO MEDICAL s.r.o. /ID# 226548 | Prague , Czechia, 120 00CCR Prague s.r.o. /ID# 226214 | Prague , Czechia, 130 00CCR Czech a.s /ID# 226270 | Prague , Czechia, 140 00FORBELI s.r.o. /ID# 226396 | Prague , Czechia, 160 00INEP medical s.r.o. /ID# 226531 | Prague , Czechia, 186 00Vestra Clinics s.r.o. /ID# 226547 | Rychnov nad Kněžnou , Czechia, 516 01NeuroMed Zlin s.r.o. /ID# 226487 | Zlín , Czechia, 760 01Rigshospitalet Glostrup /ID# 226271 | Glostrup Municipality Capital Region, Denmark, 2600CHU Nice - Hopital de Cimiez /ID# 226401 | Nice Alpes-Maritimes, France, 06000CHU Lille /ID# 226501 | Lille Nord, France, 59000CHU de SAINT ETIENNE - Hopital Nord /ID# 226397 | Saint Priest EN Jarez Pays de la Loire Region, France, 42270CHU Clermont Ferand - Hopital Gabriel Montpied /ID# 226438 | Clermont-Ferrand , France, 63000AP-HP - Hopital Lariboisière /ID# 226221 | Paris , France, 75010Universitaetsklinikum Tuebingen /ID# 226529 | Tübingen Baden-Wurttemberg, Germany, 72076Charite Universitaetsmedizin Berlin - Campus Mitte /ID# 226441 | Berlin , Germany, 10117Klinische Forschung Dresden GmbH /ID# 226194 | Dresden , Germany, 01069Praxis Dr. Gendolla /ID# 226497 | Essen , Germany, 45133Universitaetsklinikum Essen /ID# 226527 | Essen , Germany, 45147Klinische Forschung Hannover-Mitte GmbH /ID# 226195 | Hanover , Germany, 30159Universitaetsklinikum Jena Klinik fuer Neurologie /ID# 226439 | Jena , Germany, 07747Vitos Orthopaedische Klinik Kassel gemeinnuetzige GmbH /ID# 231767 | Kassel , Germany, 34131Schmerzklinik Kiel /ID# 226499 | Kiel , Germany, 24149AmBeNet GmbH /ID# 226213 | Leipzig , Germany, 04107Pharmakologisches Studienzentrum Chemnitz GmbH /ID# 226202 | Mittweida , Germany, 09648Universitaetsmedizin Rostock /ID# 226517 | Rostock , Germany, 18057Neuropoint GmbH /ID# 226377 | Ulm , Germany, 89073Neuropraxis Muenchen Sued /ID# 226216 | Unterhaching , Germany, 82008Studienzentrum Nord-West /ID# 226360 | Westerstede , Germany, 26655Intermed GmbH /ID# 226376 | Wiesbaden , Germany, 65189DKD Helios Klinik Wiesbaden /ID# 226534 | Wiesbaden , Germany, 65191Bugat Pal Korhaz /ID# 226357 | Gyöngyös Heves County, Hungary, 3200Valeomed Kft /ID# 226535 | Esztergom Komárom-Esztergom, Hungary, 2500Szent Borbala Korhaz /ID# 226400 | Tatabánya Komárom-Esztergom, Hungary, 2800Somogy Megyei Kaposi Mor Oktato Korhaz /ID# 226485 | Kaposvár Somogy County, Hungary, 7400Mind Klinika Kft. /ID# 233438 | Budapest , Hungary, 1024Clinexpert Kft /ID# 226467 | Budapest , Hungary, 1033Department of Neurology, University of Szeged /ID# 226442 | Szeged , Hungary, 6725Ospedale Ss. Filippo e Nicola /ID# 226530 | Avezzano L Aquila, Italy, 67051Fondazione Policlinico Universitario Campus Bio-Medico di Roma /ID# 226361 | Rome Lazio, Italy, 00128Univ. of Bologna-IRCCS-Istituto delle Scienze Neurologiche /ID# 226475 | Bologna , Italy, 40126Azienda Ospedaliero Universitaria Careggi /ID# 226502 | Florence , Italy, 50134Fondazione IRCCS Istituto Neurologico Carlo Besta /ID# 226399 | Milan , Italy, 20133AOU Universita degli Studi della Campania Luigi Vanvitelli /ID# 226503 | Naples , Italy, 80138Universita di Pavia /ID# 226536 | Pavia , Italy, 27100Martini Ziekenhuis /ID# 226343 | Groningen , Netherlands, 9728 NTCanisius-Wilhelmina Ziekenhuis /ID# 226488 | Nijmegen , Netherlands, 6532 SZZorgSaam Zorggroep Zeeuws-Vlaanderen /ID# 226317 | Terneuzen , Netherlands, 4535 PASolumed Centrum Medyczne /ID# 226299 | Poznan Greater Poland Voivodeship, Poland, 60-529NZOZ Vitamed /ID# 226293 | Bydgoszcz Kuyavian-Pomeranian Voivodeship, Poland, 85-079Specjalistyczne Gabinety Sp. z o.o. /ID# 226266 | Krakow Lesser Poland Voivodeship, Poland, 30-539Centrum Leczenia Padaczki i Migreny /ID# 226543 | Krakow Lesser Poland Voivodeship, Poland, 31-209Centrum Medyczne Oporow /ID# 226469 | Wroclaw Lower Silesian Voivodeship, Poland, 52-416Indywidualna Praktyka Lekarska dr hab. med. Anna Szczepanska-Szerej /ID# 226235 | Lublin Lublin Voivodeship, Poland, 20-582Duplicate_RCMed Oddzial Sochaczew /ID# 226369 | Sochaczew Masovian Voivodeship, Poland, 96-500Centrum Medyczne Pratia Gdynia /ID# 226437 | Gdynia Pomeranian Voivodeship, Poland, 81-338Silmedic Sp. z o.o. /ID# 226267 | Katowice Silesian Voivodeship, Poland, 40-282EuroMedis sp. z o.o. /ID# 226268 | Szczecin West Pomeranian Voivodeship, Poland, 70-111Gabinet Lekarski Jacek Rozniecki /ID# 226323 | Lodz Łódź Voivodeship, Poland, 90-338Bashkir State Medical University /ID# 226552 | Ufa Bashkortostan Republic, Russia, 450005Kazan State Medical University /ID# 226498 | Kazan' Tatarstan, Respublika, Russia, 420012Sbhi Cp 2 Hdm /Id# 226494 | Moscow , Russia, 117556University Headache Clinic /ID# 226435 | Moscow , Russia, 119221Cephalgolog /ID# 226541 | Moscow , Russia, 125040Hospital Unversitario Marques de Valdecilla /ID# 226239 | Santander Cantabria, Spain, 39008University Clinical Hospital of Valladolid /ID# 226528 | Valledolid Castellon, Spain, 47005Hospital Universitario Vall d'Hebron /ID# 226230 | Barcelona , Spain, 08035Hospital Santa Creu i Sant Pau /ID# 226550 | Barcelona , Spain, 08041Hospital Clinico Universitario San Carlos /ID# 226483 | Madrid , Spain, 28040Hospital Clinico Universitario de Valencia /ID# 226472 | Valencia , Spain, 46010Hospital Clinico Universitario Lozano Blesa /ID# 226395 | Zaragoza , Spain, 50009Karolinska university hospital, Huddinge /ID# 226215 | Huddinge Stockholm County, Sweden, 141 86Queen Elizabeth University Hospital /ID# 226492 | Glasgow , United Kingdom, G51 4TFRe:Cognition Health - Guildford /ID# 226539 | Guildford , United Kingdom, GU2 7YDNHS Highland /ID# 226542 | Inverness , United Kingdom, IV2 3UJLeeds Teaching Hospitals NHS Trust /ID# 226538 | Leeds , United Kingdom, LS9 7TFSt Pancras Clinical Research /ID# 226551 | London , United Kingdom, EC2Y 8EAKing's College Hospital NHS Foundation Trust /ID# 226525 | London , United Kingdom, SE5 9RSRe:Cognition Health - London /ID# 226540 | London , United Kingdom, W1G 9JF
Investigators
Study Director: ALLERGAN INC., Allergan
Study Documents (Full Text)
Documents provided by Allergan: Study Protocol  November 30, 2020Documents provided by Allergan: Statistical Analysis Plan  August 20, 2022