A Study to Evaluate the Efficacy and Safety of Eptinezumab for the Prevention of Migraine in Participants That Are Not Helped by Previous Preventive Treatments

Study Overview
=================
Brief Summary
-----------------
Evaluation of eptinezumab in the prevention of migraine in participants with unsuccessful prior preventive treatments.

Detailed Description
-----------------
The total study duration from the screening visit to the completion visit is approximately 76 weeks and includes a screening period (28-30 days), a placebo-controlled treatment period (24 weeks) and a treatment extension period (48 weeks). The participant will start treatment at the baseline visit and follow a 12-week dosing schedule with either eptinezumab (100 or 300 milligrams [mg]) or placebo by intraveneous (IV) infusion. Participants who were assigned to placebo in the placebo-controlled treatment period, will be randomly allocated to one of two treatment groups: eptinezumab 300 mg or eptinezumab 100 mg.

Official Title
-----------------
Interventional, Randomized, Double-blind, Parallel-group, Placebo-controlled Study With an Extension Period to Evaluate the Efficacy and Safety of Eptinezumab for the Prevention of Migraine in Patients With Unsuccessful Prior Preventive Treatments

Conditions
-----------------
Migraine

Intervention / Treatment
-----------------
* Drug: Eptinezumab
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: The participant has a diagnosis of migraine, with a history of chronic or episodic migraines of at least 12 months prior to the Screening Visit The participant has a migraine onset of ≤50 years of age. The participant has ≥4 migraine days per month for each month within the past 3 months prior to the Screening Visit. The participant has demonstrated compliance with the Headache eDiary by entry of data for at least 24 of the 28 days following the Screening Visit. The participant fulfils the following criteria for chronic migraine (CM) or episodic migraine (EM) in prospectively collected information in the eDiary during the screening period: For participants with CM: Migraine occurring on ≥8 days and headache occurring on >14 days For participants with EM: Migraine occurring on ≥4 days and headache occurring on ≤14 days The participant has documented evidence of treatment failure (must be supported by medical record or by physician's confirmation specific to each treatment) in the past 10 years of 2-4 different migraine preventive medications. The participant has a history of either previous or active use of triptans for migraine. Exclusion Criteria: The participant has experienced failure on a previous treatment targeting the calcitonin gene-related peptide (CGRP) pathway. The participant has a treatment failure on valproate/divalproex or botulinum toxin A/B and the treatment is not the latest preventive medication prior to study inclusion. The medication is regarded as the latest if the medication start date is after the start date of the other preventive medications and the medication stop date is after the stop date of the other preventive medications. The participant has confounding and clinically significant pain syndromes, (for example, fibromyalgia, chronic low back pain, complex regional pain syndrome). The participant has a diagnosis of acute or active temporomandibular disorder. The participant has a history or diagnosis of chronic tension-type headache, hypnic headache, cluster headache, hemicrania continua, new daily persistent headache, or unusual migraine subtypes such as hemiplegic migraine (sporadic and familial), ophthalmoplegic migraine, and migraine with neurological accompaniments that are not typical of migraine aura (diplopia, altered consciousness, or long duration). The participant has a psychiatric condition that is uncontrolled and/or untreated for a minimum of 6 months prior to the Screening Visit. Participants with a lifetime history of psychosis and/or mania in the last 5 years prior to the Screening Visit are excluded. The participant has a history of clinically significant cardiovascular disease or vascular ischaemia or thromboembolic events (for example, cerebrovascular accident, deep vein thrombosis, or pulmonary embolism). Other in- and exclusion criteria may apply

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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 will receive placebo matching to eptinezumab by IV infusion, every 12 weeks starting from Baseline (Day 0) through Week 24. | Drug: Placebo<br>* concentrate for solution for infusion, intravenously<br>|
| Experimental: Eptinezumab 100 mg<br>Participants will receive eptinezumab 100 mg by IV infusion, every 12 weeks starting from Baseline (Day 0) through Week 24. | Drug: Eptinezumab<br>* Eptinezumab, concentrate for solution for infusion 100 mg/milliliter (mL)<br>|
| Experimental: Eptinezumab 300 mg<br>Participants will receive eptinezumab 300 mg by IV infusion, every 12 weeks starting from Baseline (Day 0) through Week 24. | Drug: Eptinezumab<br>* Eptinezumab, concentrate for solution for infusion 100 mg/milliliter (mL)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Number of Monthly Migraine Days (MMDs) Averaged Over Weeks 1 to 12 | A migraine day was defined as any day the participant reported a headache that met criterion A, B, C, or D: Criterion A (all of the following criteria): lasted ≥4 hours, had ≥2 of the following: unilateral location; pulsating quality; moderate or severe pain intensity; aggravation by, or causing avoidance of, routine physical activity; and was accompanied by ≥1 of the following: nausea; vomiting; photophobia and phonophobia. Criterion B: lasted ≥30 minutes and the participant had an aura with the headache. Criterion C: lasted ≥30 minutes and met ≥2 of the following criteria: lasted ≥4 hours, had ≥2 of the following: unilateral location; pulsating quality; moderate or severe pain intensity; aggravation by, or causing avoidance of, routine physical activity, and was accompanied by ≥1 of the following: nausea; vomiting; photophobia and phonophobia. Criterion D: the participant took medication to treat the headache because he/she believed he/she was having a migraine. | Baseline, Weeks 1 - 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With ≥50% Reduction From Baseline in MMDs Averaged Over Weeks 1 to 12 | A migraine day was defined as any day the participant reported a headache that met criterion A, B, C, or D: Criterion A (all of the following criteria): lasted ≥4 hours, had ≥2 of the following: unilateral location; pulsating quality; moderate or severe pain intensity; aggravation by, or causing avoidance of, routine physical activity; and was accompanied by ≥1 of the following: nausea; vomiting; photophobia and phonophobia. Criterion B: lasted ≥30 minutes and the participant had an aura with the headache. Criterion C: lasted ≥30 minutes and met ≥2 of the following criteria: lasted ≥4 hours, had ≥2 of the following: unilateral location; pulsating quality; moderate or severe pain intensity; aggravation by, or causing avoidance of, routine physical activity, and was accompanied by ≥1 of the following: nausea; vomiting; photophobia and phonophobia. Criterion D: the participant took medication to treat the headache because he/she believed he/she was having a migraine. | Baseline to Weeks 1 - 12 | 
| Change From Baseline in the Number of MMDs Averaged Over Weeks 13 to 24 | A migraine day was defined as any day the participant reported a headache that met criterion A, B, C, or D: Criterion A (all of the following criteria): lasted ≥4 hours, had ≥2 of the following: unilateral location; pulsating quality; moderate or severe pain intensity; aggravation by, or causing avoidance of, routine physical activity; and was accompanied by ≥1 of the following: nausea; vomiting; photophobia and phonophobia. Criterion B: lasted ≥30 minutes and the participant had an aura with the headache. Criterion C: lasted ≥30 minutes and met ≥2 of the following criteria: lasted ≥4 hours, had ≥2 of the following: unilateral location; pulsating quality; moderate or severe pain intensity; aggravation by, or causing avoidance of, routine physical activity, and was accompanied by ≥1 of the following: nausea; vomiting; photophobia and phonophobia. Criterion D: the participant took medication to treat the headache because he/she believed he/she was having a migraine. | Baseline, Weeks 13 - 24 | 
| Percentage of Participants With ≥75% Reduction From Baseline in MMDs Averaged Over Weeks 1 to 12 | A migraine day was defined as any day the participant reported a headache that met criterion A, B, C, or D: Criterion A (all of the following criteria): lasted ≥4 hours, had ≥2 of the following: unilateral location; pulsating quality; moderate or severe pain intensity; aggravation by, or causing avoidance of, routine physical activity; and was accompanied by ≥1 of the following: nausea; vomiting; photophobia and phonophobia. Criterion B: lasted ≥30 minutes and the participant had an aura with the headache. Criterion C: lasted ≥30 minutes and met ≥2 of the following criteria: lasted ≥4 hours, had ≥2 of the following: unilateral location; pulsating quality; moderate or severe pain intensity; aggravation by, or causing avoidance of, routine physical activity, and was accompanied by ≥1 of the following: nausea; vomiting; photophobia and phonophobia. Criterion D: the participant took medication to treat the headache because he/she believed he/she was having a migraine. | Baseline to Weeks 1 - 12 | 
| Change From Baseline in the Headache Impact Test (HIT-6) Score at Week 12 | The HIT-6 (version 1.0) is a Likert-type, self-reporting questionnaire designed to assess the impact of an occurring headache and its effect on the ability to function normally in daily life. The HIT-6 contains 6 questions, each item was rated from never to always with the following response scores: never = 6, rarely = 8, sometimes = 10, very often = 11, and always = 13. The total score for the HIT-6 was the sum of each response score ranging from 36 to 78. The life impact derived from the total score was described as followed: severe (≥60), substantial (56-59), some (50-55), little to none (≤49). | Baseline, Week 12 | 
| Percentage of Participants With ≥50% Reduction From Baseline in MMDs Averaged Over Weeks 13 to 24 | A migraine day was defined as any day the participant reported a headache that met criterion A, B, C, or D: Criterion A (all of the following criteria): lasted ≥4 hours, had ≥2 of the following: unilateral location; pulsating quality; moderate or severe pain intensity; aggravation by, or causing avoidance of, routine physical activity; and was accompanied by ≥1 of the following: nausea; vomiting; photophobia and phonophobia. Criterion B: lasted ≥30 minutes and the participant had an aura with the headache. Criterion C: lasted ≥30 minutes and met ≥2 of the following criteria: lasted ≥4 hours, had ≥2 of the following: unilateral location; pulsating quality; moderate or severe pain intensity; aggravation by, or causing avoidance of, routine physical activity, and was accompanied by ≥1 of the following: nausea; vomiting; photophobia and phonophobia. Criterion D: the participant took medication to treat the headache because he/she believed he/she was having a migraine. | Baseline to Weeks 13 - 24 | 
| Percentage of Participants With ≥75% Reduction From Baseline in MMDs Averaged Over Weeks 13 to 24 | A migraine day was defined as any day the participant reported a headache that met criterion A, B, C, or D: Criterion A (all of the following criteria): lasted ≥4 hours, had ≥2 of the following: unilateral location; pulsating quality; moderate or severe pain intensity; aggravation by, or causing avoidance of, routine physical activity; and was accompanied by ≥1 of the following: nausea; vomiting; photophobia and phonophobia. Criterion B: lasted ≥30 minutes and the participant had an aura with the headache. Criterion C: lasted ≥30 minutes and met ≥2 of the following criteria: lasted ≥4 hours, had ≥2 of the following: unilateral location; pulsating quality; moderate or severe pain intensity; aggravation by, or causing avoidance of, routine physical activity, and was accompanied by ≥1 of the following: nausea; vomiting; photophobia and phonophobia. Criterion D: the participant took medication to treat the headache because he/she believed he/she was having a migraine. | Baseline to Weeks 13 - 24 | 
| Percentage of Participants With 100% Reduction From Baseline in MMDs Averaged Over Weeks 1 to 12 | A migraine day was defined as any day the participant reported a headache that met criterion A, B, C, or D: Criterion A (all of the following criteria): lasted ≥4 hours, had ≥2 of the following: unilateral location; pulsating quality; moderate or severe pain intensity; aggravation by, or causing avoidance of, routine physical activity; and was accompanied by ≥1 of the following: nausea; vomiting; photophobia and phonophobia. Criterion B: lasted ≥30 minutes and the participant had an aura with the headache. Criterion C: lasted ≥30 minutes and met ≥2 of the following criteria: lasted ≥4 hours, had ≥2 of the following: unilateral location; pulsating quality; moderate or severe pain intensity; aggravation by, or causing avoidance of, routine physical activity, and was accompanied by ≥1 of the following: nausea; vomiting; photophobia and phonophobia. Criterion D: the participant took medication to treat the headache because he/she believed he/she was having a migraine. | Baseline to Weeks 1 - 12 | 
| Percentage of Participants With ≥50% Reduction From Baseline in Monthly Headache Days (MHDs) Averaged Over Weeks 1 to 12 | A headache day was defined as a day with a headache that lasted ≥30 minutes or met the definition of a migraine day (as defined in criterion A, B, C, or D above in outcome measure 1). | Baseline to Weeks 1 - 12 | 
| Percentage of Participants With ≥75% Reduction From Baseline in Monthly Headache Days (MHDs) Averaged Over Weeks 1 to 12 | A headache day was defined as a day with a headache that lasted ≥30 minutes or met the definition of a migraine day (as defined in criterion A, B, C, or D above in outcome measure 1). | Baseline to Weeks 1 - 12 | 
| Percentage of Participants With 100% Reduction From Baseline in Monthly Headache Days (MHDs) Averaged Over Weeks 1 to 12 | A headache day was defined as a day with a headache that lasted ≥30 minutes or met the definition of a migraine day (as defined in criterion A, B, C, or D above in outcome measure 1). | Baseline to Weeks 1 - 12 | 
| Change From Baseline in the Number of MHDs Averaged Over Weeks 1 to 12 | A headache day was defined as a day with a headache that lasted ≥30 minutes or met the definition of a migraine day (as defined in criterion A, B, C, or D above in outcome measure 1). | Baseline, Weeks 1 - 12 | 
| Change From Baseline in the Percentage of Migraine Attacks With Severe Pain Intensity Averaged Over Weeks 1 to 12 | A migraine attack was defined as a headache that occurred on a single day or lasted >1 day and that met the criteria for a migraine day (as defined in criterion A, B, C, or D above in outcome measure 1). | Baseline, Weeks 1 - 12 | 
| Change From Baseline in the Percentage of Headache Episodes With Severe Pain Intensity Averaged Over Weeks 1 to 12 | A headache episode was defined as a headache lasted ≥30 minutes or that met the criteria for a migraine (as defined in criterion A, B, C, or D above in outcome measure 1). | Baseline, Weeks 1 - 12 | 
| Change From Baseline in the Number of Monthly Days With Use of Acute Migraine Medication Averaged Over Weeks 1 to 12 | In the evening eDiary, participants were asked each day to fill out whether they used any of the following medications during that day: Ergotamine, triptan, analgesic, opioid, or combination analgesic. A day where the participant answered that they took any of those in the evening eDiary was considered a day with use of acute migraine medication. | Baseline, Weeks 1 - 12 | 
| Change From Baseline in the Number of Monthly Days With Use of Acute Migraine Medication Averaged Over Weeks 13 to 24 | In the evening eDiary, participants were asked each day to fill out whether they used any of the following medications during that day: Ergotamine, triptan, analgesic, opioid, or combination analgesic. A day where the participant answered that they took any of those in the evening eDiary was considered a day with use of acute migraine medication. | Baseline, Weeks 13- 24 | 
| Change From Baseline in the Number of MMDs With Use of Acute Medication Averaged Over Weeks 1 to 12 | Number of MMDs with acute medication usage was derived using the answer to Did you take any medications to treat this headache? in the headache diary. The question was asked when a participant was ending a headache. Thus, a migraine day with acute medication usage was defined as a migraine day with the extra condition that this question was answered as Yes. | Baseline, Weeks 1 - 12 | 
| Change From Baseline in the Number of MMDs With Use of Acute Medication Averaged Over Weeks 13 to 24 | Number of MMDs with acute medication usage was derived using the answer to Did you take any medications to treat this headache? in the headache diary. The question was asked when a participant was ending a headache. Thus, a migraine day with acute medication usage was defined as a migraine day with the extra condition that this question was answered as Yes. | Baseline, Weeks 13 - 24 | 
| Patient Global Impression of Change (PGIC) Score at Week 12 | The PGIC is a single, participant-reported item reflecting the participant's impression of change in his/her disease status since the start of the study (that is, in relation to activity limitations, symptoms, emotions, and overall quality of life). Participants rated their impression of change in disease status on a 7-point scale (1 = very much improved; 2 = much improved; 3 = minimally improved; 4 = no change; 5 = minimally worse; 6 = much worse; 7 = very much worse) where a higher score indicated worsening. Score ranges from 1 (Very Much Improved) to 7 (Very Much Worse). Lower scores indicate better health status. | Week 12 | 
| PGIC Score at Week 24 | The PGIC is a single, participant-reported item reflecting the participant's impression of change in his/her disease status since the start of the study (that is, in relation to activity limitations, symptoms, emotions, and overall quality of life). Participants rated their impression of change in disease status on a 7-point scale (1 = very much improved; 2 = much improved; 3 = minimally improved; 4 = no change; 5 = minimally worse; 6 = much worse; 7 = very much worse) where a higher score indicated worsening. Score ranges from 1 (Very Much Improved) to 7 (Very Much Worse). Lower scores indicate better health status. | Week 24 | 
| Change From Baseline in the Number of MMDs in Participants With Medication Overuse Headache (MOH) Averaged Over Weeks 1 to 12 |  | Baseline, Weeks 1 - 12 | 
| Percentage of Participants With Migraine on the Day After First Dosing |  | Day 1 | 
| Most Bothersome Symptom (MBS) Score at Week 12 | Participants were asked about their most bothersome symptom associated with their migraines during the Baseline Visit. Participants were asked to rate the improvement in this symptom from baseline on a 7-point scale (1 = very much improved; 2 = much improved; 3 = minimally improved; 4 = no change; 5 = minimally worse; 6 = much worse; 7 = very much worse) where a high score indicated worsening. Score ranges from 1 (Very Much Improved) to 7 (Very Much Worse). Lower scores indicate better health status. The MBS areas included: nausea, vomiting, sensitivity to light, sensitivity to sound, mental cloudiness, fatigue, pain with activity, mood changes, and other symptoms. | Week 12 | 
| Change From Baseline in the HIT-6 Score at Week 24 | The HIT-6 (version 1.0) is a Likert-type, self-reporting questionnaire designed to assess the impact of an occurring headache and its effect on the ability to function normally in daily life. The HIT-6 contains 6 questions, each item was rated from never to always with the following response scores: never = 6, rarely = 8, sometimes = 10, very often = 11, and always = 13. The total score for the HIT-6 was the sum of each response score ranging from 36 to 78. The life impact derived from the total score was described as followed: severe (≥60), substantial (56-59), some (50-55), little to none (≤49). | Baseline, Week 24 | 
| Change From Baseline in the Migraine-Specific Quality of Life (MSQ) Subscores (Role Function-Restrictive, Role Function-Preventive, Emotional Function) at Week 12 | The MSQ is a participant-reported outcome designed to assess the quality of life in participants with migraine. It consists of 14 items covering 3 domains: role function restrictive (7 items); role function preventive (4 items); and emotional function (3 items). Each item was scored on a 6-point scale ranging from 1 (none of the time) to 6 (all of the time). Raw domain scores were summed and transformed to a 0- to 100-point scale. Higher scores indicated better quality of life. | Baseline, Week 12 | 
| Change From Baseline in the Health-Related Quality of Life (EQ-5D-5L) Visual Analog Scale (VAS) Score at Week 12 | The EQ-5D-5L is a participant-reported assessment designed to measure the participant's well-being. It consists of 5 descriptive items (mobility, self-care, usual activities, pain/discomfort, and depression/anxiety) and a VAS of the overall health state. Each descriptive item was rated on a 5-point index ranging from 1 (no problems) to 5 (extreme problems). The VAS ranged from 0 (worst imaginable health state) to 100 (best imaginable health state). | Baseline, Week 12 | 
| Change From Baseline in the MSQ Subscores (Role Function-Restrictive, Role Function-Preventive, Emotional Function) at Week 24 | The MSQ is a participant-reported outcome designed to assess the quality of life in participants with migraine. It consists of 14 items covering 3 domains: role function restrictive (7 items); role function preventive (4 items); and emotional function (3 items). Each item was scored on a 6-point scale ranging from 1 (none of the time) to 6 (all of the time). Raw domain scores were summed and transformed to a 0- to 100-point scale. Higher scores indicated better quality of life. | Baseline, Week 24 | 
| Change From Baseline in the Health-Related Quality of Life (EQ-5D-5L) VAS Score at Week 24 | The EQ-5D-5L is a participant-reported assessment designed to measure the participant's well-being. It consists of 5 descriptive items (mobility, self-care, usual activities, pain/discomfort, and depression/anxiety) and a VAS of the overall health state. Each descriptive item was rated on a 5-point index ranging from 1 (no problems) to 5 (extreme problems). The VAS ranged from 0 (worst imaginable health state) to 100 (best imaginable health state). | Baseline, Week 24 | 
| Change From Baseline in the Work Productivity and Activity Impairment (WPAI) Questionnaire Subscores (Absenteeism, Presenteeism, Work Productivity Loss, Activity Impairment) at Week 12 | The WPAI Questionnaire is a participant-reported instrument developed to measure the impact on work productivity and regular activities attributable to a specific health problem (migraine). Recall period is the past 7 days. It contains 6 items that measure: 1) employment status, 2) hours missed from work due to the specific health problem, 3) hours missed from work for other reasons, 4) hours actually worked, 5) degree health affected productivity while working, and 6) degree health affected productivity in regular unpaid activities. Four scores were calculated from the responses to these 6 items: absenteeism, presenteeism, work productivity loss, and activity impairment. Scores were calculated as impairment percentages (0-100%), with higher numbers indicating greater impairment and less productivity, i.e, worse outcomes. | Baseline, Week 12 | 
| Change From Baseline in the WPAI Questionnaire Subscores (Absenteeism, Presenteeism, Work Productivity Loss, Activity Impairment) at Week 24 | The WPAI Questionnaire is a participant-reported instrument developed to measure the impact on work productivity and regular activities attributable to a specific health problem (migraine). Recall period is the past 7 days. It contains 6 items that measure: 1) employment status, 2) hours missed from work due to the specific health problem, 3) hours missed from work for other reasons, 4) hours actually worked, 5) degree health affected productivity while working, and 6) degree health affected productivity in regular unpaid activities. Four scores were calculated from the responses to these 6 items: absenteeism, presenteeism, work productivity loss, and activity impairment. Scores were calculated as impairment percentages (0-100%), with higher numbers indicating greater impairment and less productivity, i.e, worse outcomes. | Baseline, Week 24 | 
| Percentage of Participants With ≥5-Point Reduction From Baseline to Week 12 in HIT-6 Score | The HIT-6 (version 1.0) is a Likert-type, self-reporting questionnaire designed to assess the impact of an occurring headache and its effect on the ability to function normally in daily life. The HIT-6 contains 6 questions, each item was rated from never to always with the following response scores: never = 6, rarely = 8, sometimes = 10, very often = 11, and always = 13. The total score for the HIT-6 was the sum of each response score ranging from 36 to 78. The life impact derived from the total score was described as followed: severe (≥60), substantial (56-59), some (50-55), little to none (≤49). | Baseline to Week 12 | 
| Percentage of Participants With ≥5-Point Reduction From Baseline to Week 24 in HIT-6 Score | The HIT-6 (version 1.0) is a Likert-type, self-reporting questionnaire designed to assess the impact of an occurring headache and its effect on the ability to function normally in daily life. The HIT-6 contains 6 questions, each item was rated from never to always with the following response scores: never = 6, rarely = 8, sometimes = 10, very often = 11, and always = 13. The total score for the HIT-6 was the sum of each response score ranging from 36 to 78. The life impact derived from the total score was described as followed: severe (≥60), substantial (56-59), some (50-55), little to none (≤49). | Baseline to Week 24 | 
| Health Care Resource Utilization (HCRU): Visits to a Family Doctor/General Practitioner | Number of participants who visited to a family doctor/general practitioner has been reported. | Week 12 | 
| HCRU: Visits to a Specialist | Number of participants who visited to a specialist has been reported. | Week 12 | 
| HCRU: Number of Emergency Department Visits Due to Your Migraine | Number of participants who visited to emergency department due to your migraine has been reported. | Week 12 | 
| HCRU: Number of Hospital Admissions Due to Migraine | Number of participants who admitted in the hospital due to migraine has been reported. | Week 12 | 
| HCRU: Total Number of Overnight Hospital Stays Due to Migraine | Number of participants who had total number of overnight hospital stays due to migraine has been reported. | Week 12 | 
| Change From Baseline in the Number of MMDs Averaged Over Weeks 25 to 36, 37 to 48, 49 to 60, and 61 to 72 | A migraine day was defined as any day the participant reported a headache that met criterion A, B, C, or D: Criterion A (all of the following criteria): lasted ≥4 hours, had ≥2 of the following: unilateral location; pulsating quality; moderate or severe pain intensity; aggravation by, or causing avoidance of, routine physical activity; and was accompanied by ≥1 of the following: nausea; vomiting; photophobia and phonophobia. Criterion B: lasted ≥30 minutes and the participant had an aura with the headache. Criterion C: lasted ≥30 minutes and met ≥2 of the following criteria: lasted ≥4 hours, had ≥2 of the following: unilateral location; pulsating quality; moderate or severe pain intensity; aggravation by, or causing avoidance of, routine physical activity, and was accompanied by ≥1 of the following: nausea; vomiting; photophobia and phonophobia. Criterion D: the participant took medication to treat the headache because he/she believed he/she was having a migraine. | Baseline, Weeks 25 - 36, 37 - 48, 49 - 60, and 61 - 72 | 
| Percentage of Participants With ≥50% Reduction From Baseline in MMDs Averaged Over Weeks 25 to 36, 37 to 48, 49 to 60, and 61 to 72 | A migraine day was defined as any day the participant reported a headache that met criterion A, B, C, or D: Criterion A (all of the following criteria): lasted ≥4 hours, had ≥2 of the following: unilateral location; pulsating quality; moderate or severe pain intensity; aggravation by, or causing avoidance of, routine physical activity; and was accompanied by ≥1 of the following: nausea; vomiting; photophobia and phonophobia. Criterion B: lasted ≥30 minutes and the participant had an aura with the headache. Criterion C: lasted ≥30 minutes and met ≥2 of the following criteria: lasted ≥4 hours, had ≥2 of the following: unilateral location; pulsating quality; moderate or severe pain intensity; aggravation by, or causing avoidance of, routine physical activity, and was accompanied by ≥1 of the following: nausea; vomiting; photophobia and phonophobia. Criterion D: the participant took medication to treat the headache because he/she believed he/she was having a migraine. | Baseline to Weeks 25 - 36, 37 - 48, 49 - 60, and 61 - 72 | 
| Percentage of Participants With ≥75% Reduction From Baseline in MMDs Averaged Over Weeks 25 to 36, 37 to 48, 49 to 60, and 61 to 72 | A migraine day was defined as any day the participant reported a headache that met criterion A, B, C, or D: Criterion A (all of the following criteria): lasted ≥4 hours, had ≥2 of the following: unilateral location; pulsating quality; moderate or severe pain intensity; aggravation by, or causing avoidance of, routine physical activity; and was accompanied by ≥1 of the following: nausea; vomiting; photophobia and phonophobia. Criterion B: lasted ≥30 minutes and the participant had an aura with the headache. Criterion C: lasted ≥30 minutes and met ≥2 of the following criteria: lasted ≥4 hours, had ≥2 of the following: unilateral location; pulsating quality; moderate or severe pain intensity; aggravation by, or causing avoidance of, routine physical activity, and was accompanied by ≥1 of the following: nausea; vomiting; photophobia and phonophobia. Criterion D: the participant took medication to treat the headache because he/she believed he/she was having a migraine. | Baseline to Weeks 25 - 36, 37 - 48, 49 - 60, and 61 - 72 | 
| Change From Baseline in HIT-6 Score at Weeks 36, 48, 60, and 72 | The HIT-6 (version 1.0) is a Likert-type, self-reporting questionnaire designed to assess the impact of an occurring headache and its effect on the ability to function normally in daily life. The HIT-6 contains 6 questions, each item was rated from never to always with the following response scores: never = 6, rarely = 8, sometimes = 10, very often = 11, and always = 13. The total score for the HIT-6 was the sum of each response score ranging from 36 to 78. The life impact derived from the total score was described as followed: severe (≥60), substantial (56-59), some (50-55), little to none (≤49). | Baseline, Weeks 36, 48, 60, and 72 |