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

Episodic Migraine Clinical Trial

— ELEVATE  

Official title:

A 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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04740827
• Other study ID #: 3101-304-002
• Secondary ID: 2019-003448-58
• Status: Completed
• Phase: Phase 3
• Start date: March 5, 2021
• Est. completion date: August 4, 2022

Study information

• Verified date: September 2023
• Source: Allergan
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will assess the safety, tolerability, and efficacy of Atogepant 60 mg compared with placebo in participants with episodic migraine and who have previously failed 2 to 4 classes of oral prophylactic treatments.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 315
• Est. completion date: August 4, 2022
• Est. primary completion date: August 4, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Episodic Migraine
• Migraine Disorders

Intervention

Drug:
• Atogepant 60 mg
Atogepant tablets.
• Placebo
Atogepant matching placebo tablets.

Locations

Country	Name	City	State
Australia	Alfred Health /ID# 226341	Melbourne	Victoria
Australia	The Royal Melbourne Hospital /ID# 226402	Parkville	Victoria
Canada	Aggarwal and Associates Limited /ID# 226321	Brampton	Ontario
Canada	Ottawa Headache Centre Research Inc /ID# 226257	Ottawa	Ontario
Canada	Diex Recherche Sherbrooke Inc. /ID# 226375	Sherbrooke	Quebec
Czechia	POLIKLINIKA CHOCEN, a.s. /ID# 226510	Chocen
Czechia	BRAIN-SOULTHERAPY s.r.o. /ID# 226489	Kladno
Czechia	CCR Ostrava, s.r.o. /ID# 226279	Ostrava
Czechia	A-SHINE s.r.o. /ID# 226208	Plzen
Czechia	FORBELI s.r.o. /ID# 226396	Prague
Czechia	CLINTRIAL s.r.o. /ID# 226192	Prague 10
Czechia	CCR Czech a.s /ID# 226270	Prague 4
Czechia	CCR Prague s.r.o. /ID# 226214	Praha
Czechia	DADO MEDICAL s.r.o. /ID# 226548	Praha
Czechia	INEP medical s.r.o. /ID# 226531	Praha
Czechia	Vestra Clinics s.r.o. /ID# 226547	Rychnov nad Kneznou
Czechia	NeuroMed Zlin s.r.o. /ID# 226487	Zlin
Denmark	Rigshospitalet Glostrup /ID# 226271	Glostrup	Hovedstaden
France	CHU Clermont Ferand - Hopital Gabriel Montpied /ID# 226438	Clermont Ferrand
France	CHU Lille /ID# 226501	Lille	Nord
France	CHU Nice - Hopital de Cimiez /ID# 226401	Nice	Alpes-Maritimes
France	AP-HP - Hopital Lariboisière /ID# 226221	Paris
France	CHU de SAINT ETIENNE - Hopital Nord /ID# 226397	St. Priest En Jarez	Loire
Germany	Charite Universitaetsmedizin Berlin - Campus Mitte /ID# 226441	Berlin
Germany	Klinische Forschung Dresden GmbH /ID# 226194	Dresden
Germany	Praxis Dr. Gendolla /ID# 226497	Essen
Germany	Universitaetsklinikum Essen /ID# 226527	Essen
Germany	Klinische Forschung Hannover-Mitte GmbH /ID# 226195	Hannover
Germany	Universitaetsklinikum Jena Klinik fuer Neurologie /ID# 226439	Jena
Germany	Vitos Orthopaedische Klinik Kassel gemeinnuetzige GmbH /ID# 231767	Kassel
Germany	Schmerzklinik Kiel /ID# 226499	Kiel
Germany	AmBeNet GmbH /ID# 226213	Leipzig
Germany	Pharmakologisches Studienzentrum Chemnitz GmbH /ID# 226202	Mittweida
Germany	Universitaetsmedizin Rostock /ID# 226517	Rostock
Germany	Universitaetsklinikum Tuebingen /ID# 226529	Tubingen	Baden-Wuerttemberg
Germany	Neuropoint GmbH /ID# 226377	Ulm
Germany	Neuropraxis Muenchen Sued /ID# 226216	Unterhaching
Germany	Studienzentrum Nord-West /ID# 226360	Westerstede
Germany	DKD Helios Klinik Wiesbaden /ID# 226534	Wiesbaden
Germany	Intermed GmbH /ID# 226376	Wiesbaden
Hungary	Clinexpert Kft /ID# 226467	Budapest
Hungary	Mind Klinika Kft. /ID# 233438	Budapest
Hungary	Valeomed Kft /ID# 226535	Esztergom	Komarom-Esztergom
Hungary	Bugat Pal Korhaz /ID# 226357	Gyöngyös	Heves
Hungary	Somogy Megyei Kaposi Mor Oktato Korhaz /ID# 226485	Kaposvár	Somogy
Hungary	Department of Neurology, University of Szeged /ID# 226442	Szeged
Hungary	Szent Borbala Korhaz /ID# 226400	Tatabanya	Komarom-Esztergom
Italy	Ospedale Ss. Filippo e Nicola /ID# 226530	Avezzano	L Aquila
Italy	Univ. of Bologna-IRCCS-Istituto delle Scienze Neurologiche /ID# 226475	Bologna
Italy	Azienda Ospedaliero Universitaria Careggi /ID# 226502	Florence
Italy	Fondazione IRCCS Istituto Neurologico Carlo Besta /ID# 226399	Milan
Italy	AOU Universita degli Studi della Campania Luigi Vanvitelli /ID# 226503	Napoli
Italy	Universita di Pavia /ID# 226536	Pavia
Italy	Fondazione Policlinico Universitario Campus Bio-Medico di Roma /ID# 226361	Rome	Lazio
Netherlands	Martini Ziekenhuis /ID# 226343	Groningen
Netherlands	Canisius-Wilhelmina Ziekenhuis /ID# 226488	Nijmegen
Netherlands	ZorgSaam Zorggroep Zeeuws-Vlaanderen /ID# 226317	Terneuzen
Poland	NZOZ Vitamed /ID# 226293	Bydgoszcz	Kujawsko-pomorskie
Poland	Centrum Medyczne Pratia Gdynia /ID# 226437	Gdynia	Pomorskie
Poland	Silmedic Sp. z o.o. /ID# 226267	Katowice	Slaskie
Poland	Centrum Leczenia Padaczki i Migreny /ID# 226543	Krakow	Malopolskie
Poland	Specjalistyczne Gabinety Sp. z o.o. /ID# 226266	Krakow	Malopolskie
Poland	Gabinet Lekarski Jacek Rozniecki /ID# 226323	Lodz	Lodzkie
Poland	Indywidualna Praktyka Lekarska dr hab. med. Anna Szczepanska-Szerej /ID# 226235	Lublin	Lubelskie
Poland	Solumed Centrum Medyczne /ID# 226299	Poznan	Wielkopolskie
Poland	Duplicate_RCMed Oddzial Sochaczew /ID# 226369	Sochaczew	Mazowieckie
Poland	EuroMedis sp. z o.o. /ID# 226268	Szczecin	Zachodniopomorskie
Poland	Centrum Medyczne Oporow /ID# 226469	Wroclaw	Dolnoslaskie
Russian Federation	Kazan State Medical University /ID# 226498	Kazan	Tatarstan, Respublika
Russian Federation	Cephalgolog /ID# 226541	Moscow
Russian Federation	Sbhi Cp 2 Hdm /Id# 226494	Moscow
Russian Federation	University Headache Clinic /ID# 226435	Moscow
Russian Federation	Bashkir State Medical University /ID# 226552	Ufa	Bashkortostan, Respublika
Spain	Hospital Santa Creu i Sant Pau /ID# 226550	Barcelona
Spain	Hospital Universitario Vall d'Hebron /ID# 226230	Barcelona
Spain	Hospital Clinico Universitario San Carlos /ID# 226483	Madrid
Spain	Hospital Unversitario Marques de Valdecilla /ID# 226239	Santander	Cantabria
Spain	Hospital Clinico Universitario de Valencia /ID# 226472	Valencia
Spain	University Clinical Hospital of Valladolid /ID# 226528	Valledolid	Castellon
Spain	Hospital Clinico Universitario Lozano Blesa /ID# 226395	Zaragoza
Sweden	Karolinska university hospital, Huddinge /ID# 226215	Huddinge	Stockholms Lan
United Kingdom	Queen Elizabeth University Hospital /ID# 226492	Glasgow
United Kingdom	Re:Cognition Health - Guildford /ID# 226539	Guildford
United Kingdom	NHS Highland /ID# 226542	Inverness
United Kingdom	Leeds Teaching Hospitals NHS Trust /ID# 226538	Leeds
United Kingdom	King's College Hospital NHS Foundation Trust /ID# 226525	London
United Kingdom	Re:Cognition Health - London /ID# 226540	London
United Kingdom	St Pancras Clinical Research /ID# 226551	London
United States	Albuquerque Clinical Trials, Inc /ID# 233445	Albuquerque	New Mexico
United States	Austin Clinical Trial Partners /ID# 228387	Austin	Texas
United States	FutureSearch Trials of Neurology /ID# 226423	Austin	Texas
United States	Pharmasite Research, Inc. /ID# 226445	Baltimore	Maryland
United States	Northwest Clinical Research Center /ID# 226228	Bellevue	Washington
United States	Alpine Clinical Research Center /ID# 226201	Boulder	Colorado
United States	DiscoveResearch, Inc /ID# 226491	Bryan	Texas
United States	CTI Clinical Trial and Consulting /ID# 226281	Cincinnati	Ohio
United States	Axiom Research /ID# 226379	Colton	California
United States	FutureSearch Trials of Dallas, LP /ID# 226493	Dallas	Texas
United States	Pharmacology Research Institute (PRI) - Encino (Wake) /ID# 226434	Encino	California
United States	Allied Physicians - Fort Wayne Neurological Center /ID# 226350	Fort Wayne	Indiana
United States	Methodist Physicians Clinic /ID# 226470	Fremont	Nebraska
United States	Pharmacology Research Institute (PRI) - Los Alamitos (Wake) /ID# 226388	Los Alamitos	California
United States	Pharmacology Research Institute (PRI) - Los Alamitos (Wake) /ID# 226405	Los Alamitos	California
United States	Velocity Clinical Research - Boise /ID# 226320	Meridian	Idaho
United States	Deaconess Clinic - Gateway Health Center /ID# 226481	Newburgh	Indiana
United States	Excell Research, Inc /ID# 228386	Oceanside	California
United States	Sensible Healthcare /ID# 226197	Ocoee	Florida
United States	LinQ Research, LLC /ID# 226227	Pearland	Texas
United States	Amici Clinical Research - Raritan /ID# 226282	Raritan	New Jersey
United States	StudyMetrix Research /ID# 226297	Saint Peters	Missouri
United States	Meridien Research /ID# 226224	Saint Petersburg	Florida
United States	Meridien Research /ID# 226302	Saint Petersburg	Florida
United States	Highland Clinical Research /ID# 226288	Salt Lake City	Utah
United States	Clinvest Research LLC /ID# 226273	Springfield	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Allergan

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Czechia,  Denmark,  France,  Germany,  Hungary,  Italy,  Netherlands,  Poland,  Russian Federation,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Baseline to Week 12
Primary	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.	Baseline to Week 12
Secondary	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.	Baseline to Week 12
Secondary	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.	Baseline to Week 12
Secondary	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.	Baseline to Week 12
Secondary	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.	Baseline to Week 12
Secondary	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.	Baseline to Week 12
Secondary	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.	Baseline to Week 12
Secondary	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.	Baseline to Week 12
Secondary	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.	Baseline to Week 12
Secondary	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).	Baseline to Week 12
Secondary	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).	Baseline to Week 12
Secondary	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.	Baseline to Week 12
Secondary	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.	From first dose of study drug until 30 days after last dose of study drug (up to Week 12)