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

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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Episodic Migraine

Intervention / Treatment
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* Drug: Atogepant 60 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Participants received atogepant-matching placebo tablets, orally, once daily (QD) for up to 12 weeks in a double-blind (DB) treatment period. | Drug: Placebo<br>* Atogepant matching placebo tablets.<br>|
| Active Comparator: Atogepant 60 mg<br>Participants received atogepant 60 mg, orally, QD for up to 12 weeks in a DB treatment period. | Drug: Atogepant 60 mg<br>* Atogepant tablets.<br>|

What is the study measuring?
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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. Mixed-effects model for repeated measures (MMRM) was used for analysis. | Baseline to Week 12 | 
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Episodic migraine