12-Week Placebo-controlled Study of Atogepant for the Preventive Treatment of Migraine in Participants With Episodic Migraine

Study Overview
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Brief Summary
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To evaluate the safety and tolerability of atogepant 30 mg and 60 mg once a day for the prevention of migraine in participants with episodic migraine.

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 Prevention of Migraine in Participants With Episodic Migraine (ADVANCE)

Conditions
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Episodic Migraine

Intervention / Treatment
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* Drug: Atogepant
* 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. Age of the participant at the time of migraine onset <50 years. Exclusion Criteria: Has a history of migraine accompanied by diplopia or decreased level of consciousness or retinal migraine. Has a current diagnosis of chronic migraine, new persistent daily headache, trigeminal autonomic cephalgia (e.g., 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. Participants with clinically significant hematologic, endocrine, cardiovascular, pulmonary, renal, hepatic, gastrointestinal, or neurologic disease.

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo-matching atogepant tablets orally once daily for 12 weeks. | Drug: Placebo<br>* Placebo-matching atogepant tablets<br>|
| Experimental: Atogepant 10 mg<br>Atogepant 10 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks. | Drug: Atogepant<br>* Atogepant tablet<br>Drug: Placebo<br>* Placebo-matching atogepant tablets<br>|
| Experimental: Atogepant 30 mg<br>Atogepant 30 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks. | Drug: Atogepant<br>* Atogepant tablet<br>Drug: Placebo<br>* Placebo-matching atogepant tablets<br>|
| Experimental: Atogepant 60 mg<br>Atogepant 60 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks. | Drug: Atogepant<br>* Atogepant tablet<br>Drug: Placebo<br>* Placebo-matching 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 the 12-Week Treatment Period | Participants recorded daily duration of migraine in a diary. A migraine day was any calendar day on which the participant experienced a migraine headache qualified by duration or acute symptomatic medication use. The monthly (4-week) migraine days was 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 was defined as the number of migraine days during the last 28 days of the Baseline phase, from Day -28 to -1. Negative change from Baseline indicates improvement. A Mixed-effects model for repeated measures (MMRM) was used for analysis. | Baseline (Day -28 to Day -1) to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Mean Monthly Headache Days Across the 12-Week Treatment Period | 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 qualified by duration or acute symptomatic medication use. 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 was defined as the number of migraine days during the last 28 days of the Baseline phase, from Day -28 to -1. Negative change from Baseline indicates improvement. MMRM was used for analysis. | Baseline (Day-28 to Day -1) to Week 12 | 
| Change From Baseline in Mean Monthly Acute Medication Use Days Across the 12-Week Treatment Period | Participants recorded allowed medication(s) to treat an acute migraine in the daily diary. The monthly (4-week) acute medication use days was 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 was defined as the number of acute medication use days during the last 28 days of the Baseline phase, from Day -28 to -1. A negative change from Baseline indicates improvement. MMRM was used for the analysis. | Baseline (Day-28 to Day -1) to Week 12 | 
| Percentage of Participants With at Least a 50% Reduction (Improvement) 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 qualified by duration or acute symptomatic medication use. 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. Each 4-week period was averaged. | Baseline (Day -28 to Day -1) 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 | 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 three domains: role function-restrictive (questions 1-7, score range 7 to 42) assesses how migraines limit one's daily social and work-related activities; role function-preventive (questions 8-11, score ranges 4 to 24) assesses how migraines prevent these activities; and the emotional function (questions 12-14, score ranges 3 to 18) domain assesses the emotions associated with migraines. Participants respond to items using a 6-point scale where 1=none of the time and 6=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 from Baseline indicate better quality of life. MMRM was used for the analysis. | Baseline (Day 1) 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 | The AIM-D is a 9-item PRO measure that assesses the impact of migraine on the performance of daily activities and physical impairment 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 was defined as the monthly (averaged for a month) performance of daily activities domain score during the last 28 days of the Baseline period from Day -28 to -1. MMRM was used for the analysis. | Baseline (Day -28 to Day -1) to Week 12 | 
| Change From Baseline in Mean Monthly Physical Impairment Domain Score of the Activity Impairment in Migraine- Diary (AIM-D) Across the 12-Week Treatment Period | The AIM-D is a 9-item PRO measure that assesses the impact of migraine on the performance of daily activities and physical impairment 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 was defined as the monthly (averaged for a month) physical impairment domain score during the last 28 days of the Baseline period from Day -28 to -1. MMRM was used for the analysis. | Baseline (Day -28 to Day -1) to Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Migraine, Aura