A Study Using Botulinum Toxin Type A as Headache Prophylaxis for Migraine Patients With Frequent Headaches

Study Overview
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Brief Summary
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This is a 60 week study including a double-blind phase followed by an open-label phase.

Conditions
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Migraine Disorders

Intervention / Treatment
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* Biological: Botulinum Toxin Type A
* Other: placebo (saline)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Frequent migraine (>=15 headache days per month) >=4 distinct headache episodes lasting >=4 hours >=50% of baseline headache days migraine/probable migraine days Exclusion Criteria: Previous use of botulinum toxin of any serotype or immunization to any botulinum toxin serotype Any medical condition that puts the patient at increased risk with exposure to BOTOX Diagnosis of complicated migraine, chronic tension-type headache, hypnic headache, hemicrania continua, new daily persistent headache Use of prophylactic headache medication within 28 days prior to week -4 Unremitting headache lasting continuously throughout the 4-week baseline period Known or suspected TMD Diagnosis of fibromyalgia Beck depression inventory score >24 at week-4 Psychiatric problems that may have interfered with study participation

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: botulinum toxin Type A<br>Two treatment sessions in the double-blind phase and three treatment sessions in the open-label extension phase. Total minimum dose is 155 U with 31 fixed-site, fixed dose injections across seven specific head/neck muscle areas with the total maximum dose of 195 U with 39 head/neck injections. | Biological: Botulinum Toxin Type A<br>* Two treatment sessions in the double-blind phase and three treatment sessions in the open-label phase. Total minimum dose is 155 U with 31 fixed-site, fixed dose injections across seven specific head/neck muscle areas with the total maximum dose of 195 U with 39 head/neck injections.<br>* Other names: BOTOX®;|
| Placebo Comparator: Placebo (saline)<br>Two treatment sessions in the double-blind phase. Total minimum dose in 155 U with 31 fixed-site, fixed dose injections across seven specific head/neck muscle areas and the total maximum dose is 195 U with 39 head/neck injections. | Other: placebo (saline)<br>* Two treatment sessions in the double-blind phase. Total minimum dose in 155 U with 31 fixed-site, fixed dose injections across seven specific head/neck muscle areas and the total maximum dose is 195 U with 39 head/neck injections.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Frequency of Headache Days | Mean change from baseline in frequency (number) of headache days during the 28 day period ending with Week 24. Headache day defined as a calendar day [00:00 to 23:59] for which the patient reported >= 4 continuous hours of headache. | Baseline, Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Total Cumulative Hours of Headache Occurring on Headache Days | Mean change from baseline in total cumulative hours of headache occurring on headache days during the 28 day period ending with Week 24. Headache day defined as a calendar day [00:00 to 23:59] when the patient reported >= 4 continuous hours of headache. | Baseline, Week 24 | 
| Change in Frequency of Moderate/Severe Headache Days | Mean change from baseline in frequency (number) of moderate/severe headache days during the 28 day period ending with Week 24. Those calendar days with >= 4 continuous hours of headache were selected. As per the patient diary, all headache episodes occurring during those days with a maximum severity of moderate or severe were counted. | Baseline, Week 24 | 
| Change in Frequency of Migraine/Probable Migraine Headache Days | Mean change from baseline in frequency (number) of migraine/probable migraine headache days during the 28 day period ending with Week 24. Headache day defined as a calendar day with >= 4 continuous hours of headache meeting the ICHD-II criteria for migraine or probable migraine. | Baseline, Week 24 | 
| Change in Frequency of Headache Episodes | Mean change from baseline in frequency (number) of headache episodes during the 28 day period ending with Week 24. Headache episode defined as patient-reported headache with a start and stop time indicating that the pain lasted >= 4 continuous hours. | Baseline, Week 24 | 
| Percentage of Patients With Severe HIT-6 Impact Category Scores | Percentage of patients with a severe (60-78) score on the Headache Impact Test (HIT-6) Questionnaire during the 28 day period, ending with Week 24. The HIT-6 consisted of 6 questions about headache and impact on the patient's health and well-being. Answers for each question ranged from 6=Never, 8=Rarely, 10=Sometimes, 11=Very Often, and 13=Always. The total scores ranged from 36-49 (Little or No Impact), 50-55 (Some Impact), 56-59 (Substantial Impact) and 60-78 (Severe Impact). | Week 24 |