Pilot Study to Compare Frovatriptan vs. Topiramate for Prevention of Migraine

Study Overview
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Brief Summary
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Subjects enrolled at 2 investigative sites will complete 3 visits. Following Visit 1, during a 1-month Baseline Period, subjects will treat with their usual medication and document any warning signs (Prodrome pre-headache) that a migraine will occur. Following randomization (like a flip of the coin) at Visit 2, subjects will treat daily with topiramate or during Prodrome with frovatriptan. Subjects complete a 2-month Treatment Period before exit at Visit 3.This study will compare the effectiveness of daily treatment vs. treatment during the pre-headache phase for prevention of migraine.

Official Title
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A Randomized, Single-Blind Pilot Study to Compare the Efficacy and Cost-Effectiveness of Frovatriptan vs. Topiramate for the Prevention of Migraine

Conditions
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Migraine

Intervention / Treatment
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* Drug: topiramate
* Drug: frovatriptan


Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA Subject has at least a one-year history of migraine with or without aura meeting International Headache Society criteria (see Appendix) Subject has a 3-month history of averaging 3-6 migraines per month Subject reports premonitory symptoms and the ability to predict at least 50% of high impact headaches Subjects must currently or have in the past successfully utilized a triptan as an acute treatment for migraine as determined by the investigator. Male or female at least 18 years of age Subject of childbearing potential agrees to use adequate contraception during the study. Adequate methods of contraception are to be determined by the investigator and should be consistent with contraceptive care administered in the regular clinical use of frovatriptan and topiramate. Subject is aware of prodrome symptoms that may include physiological, psychological or cognitive changes. These may include, but are not limited to such symptoms as Pre-Menstrual Syndrome (PMS), change in mood, energy level, appetite, food craving, nausea, sense of hearing, sense of smell or swelling/fluid retention, excessive yawning, head pain, muscle pain/tenderness, irritability, confusion, extreme sleepiness, impaired speech or impaired memory. (The subject should be able to differentiate these symptoms from other similar symptoms that do not precede migraine). The symptoms should precede migraine by 4-24 hours signaling an impending migraine attack. Subject is able to understand instructions for the study and complete the diary Subject is willing to give informed consent to participate in the study Any migraine prophylactic medication must have a stabilized dosage for one month EXCLUSION CRITERIA History of any medical condition that would confound the results of the study including but not limited to the following: Hepatic disease or significant hepatic dysfunction History of pancreatitis History of thrombocytopenia History of glaucoma History of osteoporosis or osteopenia Cardiovascular Disease - Coronary artery disease, Ischemic heart disease or Significant Arrhythmia History of active Cerebrovascular Disease Hypertension - Uncontrolled hypertension in a non-migrainous state (> 160 mmHg systolic or >95 mmHg. diastolic). Hypertension must be controlled effectively with medication for a period of 3 months. Basilar or Hemiplegic Migraine Significant peripheral vascular disease or Raynaud's Syndrome Significant Active Renal, Hepatic, Gastrointestinal, Endocrine or Neurological Disease History of depression, mood problems or suicidal thoughts or behavior that in the opinion of the Investigator would interfere with participation in the study. History of ergotamine, triptan, or analgesic abuse within past 3 months History of current or recent drug or alcohol abuse that would interfere with participation in the study. More than 15 headache days per month within past 3 months. Women who are pregnant or breast feeding Subjects with known hypersensitivity or intolerance to topiramate or any triptan-like medication Subject is scheduled for surgical procedure to occur while enrolled in study.that in opinion of the Investigator would interfere with participation in the study. Subject is on a ketogenic diet Participation in another investigative drug study within the previous 30 days Excluded medications: MAO Inhibitors, lithium, methylergonovine, methysergide, ergotamine-containing products, or topiramate daily for migraine prophylaxis.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: topiramate<br>Subjects randomized to Group A at Visit 2 were provided with topiramate, titrated over 4 weeks to a maximum dose of 100 mg daily. One dosage adjustment was allowed with a minimum dose of 50 mg daily. | Drug: topiramate<br>* topiramate 25mg 1 tab in PM x 1 week topiramate 25mg 1 tab in AM / 1 tab in PM x 1 week topiramate 25mg 1 tab in AM / 2 tabs in PM x 1 week topiramate 25mg 2 tabs in AM / 2 tabs in PM x 5 weeks<br>* Other names: Topamax;|
| Active Comparator: frovatriptan<br>Subjects randomized to Group B at Visit 2 were provided with frovatriptan 5 mg to treat during prodrome at the point they were confident a disabling migraine would occur (before the onset of headache). | Drug: frovatriptan<br>* frovatriptan 5mg tab during premonitory phase of migraine<br>* Other names: Frova;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Migraine Attacks in Participants Using Frovatriptan in a Preemptive Treatment Paradigm vs. Daily Topiramate | Compare number of migraine attacks reported by participants using frovatriptan in a preemptive treatment paradigm vs. daily topiramate during Treatment Period Month 2 | Treatment Month 2 | 
| Number of Headache Days Reported by Participants Using Frovatriptan in a Preemptive Treatment Paradigm vs. Daily Topiramate to Prevent Migraine | Measure the change in number of headache days between participants using frovatriptan in a preemptive treatment paradigm vs. daily topiramate to prevent migraine | Treatment Month 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Headache Days Each Month Following Initiation of Treatment With Study Medication | Measure the change in number of headache days reported by participants during each treatment month following initiation of treatment with study medication | 2 Months | 
| Participants With Greater Than 50% Reduction in Migraine Attacks and Headache Days Per Month Utilizing Each Treatment Paradigm | Compare number of participants with greater than 50% reduction in migraine attacks and headache days from Baseline to Treatment Months 1 and 2 | 2 Months | 
| Quality of Life in Subjects Utilizing Each Treatment Paradigm | Quality of Life is measured by the Migraine Specific Quality of Life Questionnaire (MSQ), which includes 3 dimensions: Role Function Restrictive (degree to which performance of daily activities is limited), Role Function Preventive (degree to which performance of daily activities is interrupted), and Emotional Function (frustration and helplessness due to migraine). Scores range from 0 to 100. For each dimension, a higher score indicates a better health status. Participants completed the MSQ at Randomization, and after Treatment Months 1 and 2. | Randomization, End of Treatment Month 1, End of Treatment Month 2 | 
| Participant Satisfaction With Study Medications | Participant satisfaction is measured by the Patient Perception of Migraine Questionnaire (PPMQ). Questions were categorized within 6 dimensions: Efficacy, Functionality, Ease of Use, Cost, Bothersomeness of Side Effects, and Total Score. Scores range from 0 to 100. Higher scores represent better satisfaction. Participants completed the PPMQ 24 hours following each first dose of frovatriptan. | Treatment Month 2 | 
| Adverse Events Associated With Study Medications | Includes Adverse Events at or above 5% frequency per group. | Treatment Months 1 and 2 | 
| Cost of Frovatriptan vs. Topiramate as Preventive Treatment of Migraine | Average cost of study medication taken by each subject. Measured in dollars. | Treatment Months 1 and 2 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Migraine, Migraine prevention, Prodrome, Premonitory phase, Preemptive therapy