Efficacy and Safety Study of BOTOX® Compared to Topiramate for the Prevention of Chronic Migraine in Adults

Study Overview
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Brief Summary
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This study will evaluate the efficacy, safety and tolerability of prophylactic (preventative) treatment with BOTOX® (onabotulinumtoxinA) compared to topiramate in adults with chronic migraine.

Official Title
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A Multicenter, Prospective, Randomized, Open-label Study to Compare the Efficacy, Safety, and Tolerability of BOTOX® and Topiramate for Headache Prophylaxis in Adults With Chronic Migraine

Conditions
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Migraine Disorders

Intervention / Treatment
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* Biological: onabotulinumtoxinA
* Drug: Topiramate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: History of chronic migraine More than 15 headache days in a 28 day period (headaches that last more than 4 hours and/or require treatment with prescription medication). Exclusion Criteria: Taking opioid-containing products for acute headache treatment more than 8 days during a 28-day period Previous treatment with botulinum toxin of any serotype for any reason Previous treatment with topiramate On a ketogenic diet (high in fat, low in carbohydrates) History of acute myopia or increased intraocular pressure Diagnosis of myasthenia gravis, Eaton-Lambert syndrome, amyotrophic lateral sclerosis or any other significant disease that might interfere with neuromuscular function Acupuncture, transcutaneous electrical stimulation (TENS), cranial traction, dental splints for headache, or injection of anesthetics/steroids in the 4 weeks prior to screening.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: BOTOX®<br>155U onabotulinumtoxinA (BOTOX®) total dose per treatment by intramuscular injection every 12 weeks for up to 3 treatments. | Biological: onabotulinumtoxinA<br>* 155U onabotulinumtoxinA (BOTOX®) total dose per treatment by intramuscular injection every 12 weeks.<br>* Other names: botulinum toxin Type A;|
| Active Comparator: Topiramate<br>Topiramate starting at a daily oral dose of 25 mg/day titrated up to a maximum dose of 100 mg/day for 36 weeks. Participants who discontinue topiramate are eligible to receive treatment with BOTOX®. | Drug: Topiramate<br>* Topiramate up to a maximum oral dose of 100 mg/day.<br>* Other names: Topamax®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With a ≥ 50% Decrease From Baseline in the Frequency of Headache Days | Participants recorded their headaches in a daily e-diary. A headache day was defined as a calendar day (00:00 to 23:59) with 4 or more hours of headache and/or headache of any duration with the use of migraine-specific acute headache medication(s). The number of headache days over the 28-day period was counted. The percentage of participants with a ≥ 50% decrease in headache days in the 28-day period prior to Week 32 relative to Baseline (28-day period prior to Day 1) is reported. | Baseline (First 28 days from Screening) to the last 28-day period ending with Week 32 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Frequency of Headache Days Per 28-day Period | Participants recorded their headaches in a daily e-diary. A headache day was defined as a calendar day (00:00 to 23:59) with 4 or more hours of headache and/or headache of any duration with the use of migraine-specific acute headache medication(s). The number of headache days over the 28-day period was counted. A negative change from Baseline (less headache days) indicates improvement. | Baseline (First 28 days from Screening) to the last 28-day period ending with Week 32 | 
| Change From Baseline in Headache Impact Test (HIT-6) Total Score | The HIT-6 is a valid disease-targeted measure used to assess the impact of headaches, comprised of 6 items that assess pain, role functioning, social functioning, cognitive functioning, vitality, and psychological distress. A total score is created by summingacross all items, and ranges from 36 (no impact) to 78 (severe impact) reflecting a best to worst scoring. A negative change from Baseline (a lower score) indicates improvement. | Baseline (Day 1) to the last 28-day period ending with Week 30 | 
| Percentage of Participants With a ≥ 70% Decrease From Baseline in the Frequency of Headache Days | Participants recorded their headaches in a daily e-diary. A headache day was defined as a calendar day (00:00 to 23:59) with 4 or more hours of headache and/or headache of any duration with the use of migraine-specific acute headache medication(s). The number of headache days over the 28-day period was counted. The percentage of participants with a ≥ 70% decrease in headache days in the 28-day period prior to Week 32 relative to Baseline (28-day period prior to Day 1) is reported. | Baseline (First 28 days from Screening) to the last 28-day period ending with Week 32 |