Efficacy, Safety, and Tolerability of Multiple Dosing Regimens of Oral Atogepant (AGN-241689) in Episodic Migraine Prevention

Study Overview
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Brief Summary
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This study will evaluate the safety and tolerability of the following doses of atogepant (AGN-241689): 10 mg once daily (QD), 30 mg QD, 30 mg twice daily (BID), 60 mg QD, and 60 mg BID for the prevention of episodic migraine and will characterize the dose/response relationship.

Official Title
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A Phase 2/3, Multicenter, Randomized, Double-Blind, Placebo Controlled, Parallel-Group Study To Evaluate The Efficacy, Safety, And Tolerability Of Multiple Dosing Regimens Of Oral AGN-241689 In Episodic Migraine Prevention

Conditions
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Migraine, With or Without Aura

Intervention / Treatment
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* Drug: Atogepant
* Drug: Placebo-matching Atogepant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has at least a 1-year history of migraine with or without aura Age of the patient at the time of migraine onset < 50 years History of 4 to 14 migraine days (migraine/probable migraine headache days) per month on average in the 3 months prior to Visit 1 in the Investigator's judgment Demonstrated compliance with e-diary Exclusion Criteria: Has a history of migraine accompanied by diplopia or decreased level of consciousness and retinal migraine Has a current diagnosis of chronic migraine, new persistent daily headache, trigeminal autonomic cephalgia (eg, cluster headache), or painful cranial neuropathy Difficulty distinguishing migraine headache from other headaches Has a history of malignancy in the prior 5 years, except for adequately treated basal cell or squamous cell skin cancer, or in situ cervical cancer Has a history of gastric or small intestinal surgery, or has a disease that causes malabsorption Has a history of hepatitis within previous 6 months Usage of opioids or barbiturates > 2 days/month, triptans or ergots ≥ 10 days/month, or simple analgesics (eg, aspirin, non-steroidal anti-inflammatory drugs [NSAIDs], acetaminophen) ≥ 15 days/month in the 3 months prior to Visit 1 Pregnant or nursing females

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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 capsule orally twice daily in the morning and in the evening for 12 weeks. | Drug: Placebo-matching Atogepant<br>* Placebo-matching atogepant capsule.<br>|
| Experimental: Atogepant 10 mg QD<br>Atogepant 10 mg capsule orally once daily (QD) in the morning and one placebo-matching atogepant capsule orally once daily in the evening for 12 weeks. | Drug: Atogepant<br>* Atogepant capsule.<br>* Other names: AGN-241689;Drug: Placebo-matching Atogepant<br>* Placebo-matching atogepant capsule.<br>|
| Experimental: Atogepant 30 mg QD<br>Atogepant 30 mg capsule orally once daily in the morning and one placebo-matching atogepant capsule orally once daily in the evening for 12 weeks. | Drug: Atogepant<br>* Atogepant capsule.<br>* Other names: AGN-241689;Drug: Placebo-matching Atogepant<br>* Placebo-matching atogepant capsule.<br>|
| Experimental: Atogepant 30 mg BID<br>Atogepant 30 mg capsule orally twice daily (BID); 1 capsule in the morning and 1 capsule in the evening for 12 weeks. | Drug: Atogepant<br>* Atogepant capsule.<br>* Other names: AGN-241689;|
| Experimental: Atogepant 60 mg QD<br>Atogepant 60 mg capsule orally once daily in the morning and one placebo-matching atogepant capsule orally in the evening for 12 weeks. | Drug: Atogepant<br>* Atogepant capsule.<br>* Other names: AGN-241689;Drug: Placebo-matching Atogepant<br>* Placebo-matching atogepant capsule.<br>|
| Experimental: Atogepant 60 mg BID<br>Atogepant 60 mg capsule orally twice daily; 1 capsule in the morning and 1 capsule in the evening for 12 weeks. | Drug: Atogepant<br>* Atogepant capsule.<br>* Other names: AGN-241689;|

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 (Migraine/Probable Migraine Headache 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 and acute symptomatic medication use. The 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. Negative change from Baseline indicates improvement. | Baseline (First 28 Days of Screening/Baseline Period) 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 and acute symptomatic medication use. The 4-week (monthly) headache days was 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. Negative change from Baseline indicates improvement. | Baseline (First 28 Days of Screening/Baseline Period) to Week 12 | 
| Percentage of Participants With at Least a 50% Reduction in Mean Monthly Migraine Days (Migraine/Probable Migraine Headache 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 and acute symptomatic medication use. The 4-week migraine days=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 (First 28 Days of Screening/Baseline Period) 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 4-week (monthly) 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. A negative change from Baseline indicates improvement. | Baseline (First 28 Days of Screening/Baseline Period) to Week 12 |