Migraine
Conditions
Keywords
Migraine, Migraine prevention, Prodrome, Premonitory phase, Preemptive therapy
Brief summary
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.
Interventions
DRUGtopiramate
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
DRUGfrovatriptan
frovatriptan 5mg tab during premonitory phase of migraine
Sponsors
Endo Pharmaceuticals
Clinvest
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
1. Subject has at least a one-year history of migraine with or without aura meeting International Headache Society criteria (see Appendix) 2. Subject has a 3-month history of averaging 3-6 migraines per month 3. Subject reports premonitory symptoms and the ability to predict at least 50% of high impact headaches 4. Subjects must currently or have in the past successfully utilized a triptan as an acute treatment for migraine as determined by the investigator. 5. Male or female at least 18 years of age 6. 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. 7. 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. 8. Subject is able to understand instructions for the study and complete the diary 9. Subject is willing to give informed consent to participate in the study 10. Any migraine prophylactic medication must have a stabilized dosage for one month
Exclusion criteria
1. 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. 2. History of ergotamine, triptan, or analgesic abuse within past 3 months 3. History of current or recent drug or alcohol abuse that would interfere with participation in the study. 4. More than 15 headache days per month within past 3 months. 5. Women who are pregnant or breast feeding 6. Subjects with known hypersensitivity or intolerance to topiramate or any triptan-like medication 7. 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. 8. Subject is on a ketogenic diet 9. Participation in another investigative drug study within the previous 30 days 10. Excluded medications: MAO Inhibitors, lithium, methylergonovine, methysergide, ergotamine-containing products, or topiramate daily for migraine prophylaxis.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Migraine Attacks in Participants Using Frovatriptan in a Preemptive Treatment Paradigm vs. Daily Topiramate | Treatment Month 2 | Compare number of migraine attacks reported by participants using frovatriptan in a preemptive treatment paradigm vs. daily topiramate during Treatment Period Month 2 |
| Number of Headache Days Reported by Participants Using Frovatriptan in a Preemptive Treatment Paradigm vs. Daily Topiramate to Prevent Migraine | Treatment Month 2 | Measure the change in number of headache days between participants using frovatriptan in a preemptive treatment paradigm vs. daily topiramate to prevent migraine |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Quality of Life in Subjects Utilizing Each Treatment Paradigm | Randomization, End of Treatment Month 1, End of Treatment Month 2 | 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. |
| Participant Satisfaction With Study Medications | Treatment Month 2 | 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. |
| Number of Headache Days Each Month Following Initiation of Treatment With Study Medication | 2 Months | Measure the change in number of headache days reported by participants during each treatment month following initiation of treatment with study medication |
| Cost of Frovatriptan vs. Topiramate as Preventive Treatment of Migraine | Treatment Months 1 and 2 | Average cost of study medication taken by each subject. Measured in dollars. |
| Adverse Events Associated With Study Medications | Treatment Months 1 and 2 | Includes Adverse Events at or above 5% frequency per group. |
| Participants With Greater Than 50% Reduction in Migraine Attacks and Headache Days Per Month Utilizing Each Treatment Paradigm | 2 Months | Compare number of participants with greater than 50% reduction in migraine attacks and headache days from Baseline to Treatment Months 1 and 2 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Topiramate Subjects randomized to Group A were provided with topiramate 25mg to titrate to a maximum dosage of 100mg during Month 1. One dose adjustment was allowed with 50mg/day the required minimum dosage. Group A subjects treated with daily topiramate during Months 2 and 3 and rescued any migraine headache that occurred with frovatriptan 2.5mg. | 28 |
| Frovatriptan Subjects randomized to Group B were provided with frovatriptan 5mg to be utilized during prodrome at the point they were confident a disabling migraine would occur but before the onset of headache. Subjects were provided with frovatriptan 2.5mg for rescue of persistent or recurring headache between 4 and 24 hours following treatment during prodrome. | 27 |
| Total | 55 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 5 | 1 |
| Overall Study | Lack of Efficacy | 1 | 2 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Physician Decision | 1 | 0 |
Baseline characteristics
| Characteristic | Frovatriptan | Topiramate | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 27 Participants | 28 Participants | 55 Participants |
| Age Continuous | 37.33 years STANDARD_DEVIATION 9.46 | 37.61 years STANDARD_DEVIATION 10.3 | 37.47 years STANDARD_DEVIATION 9.82 |
| Region of Enrollment United States | 27 participants | 28 participants | 55 participants |
| Sex: Female, Male Female | 21 Participants | 22 Participants | 43 Participants |
| Sex: Female, Male Male | 6 Participants | 6 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 17 / 28 | 5 / 27 |
| serious Total, serious adverse events | 0 / 28 | 0 / 27 |
Outcome results
Primary
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
Time frame: Treatment Month 2
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Topiramate | Number of Headache Days Reported by Participants Using Frovatriptan in a Preemptive Treatment Paradigm vs. Daily Topiramate to Prevent Migraine | 4.75 Headache Days | Standard Deviation 2.59 |
| Frovatriptan | Number of Headache Days Reported by Participants Using Frovatriptan in a Preemptive Treatment Paradigm vs. Daily Topiramate to Prevent Migraine | 2.79 Headache Days | Standard Deviation 3.26 |
Primary
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
Time frame: Treatment Month 2
Population: Number of Units Analyzed is equivalent to number of migraine attacks reported during 2nd Treatment Month.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Topiramate | Number of Migraine Attacks in Participants Using Frovatriptan in a Preemptive Treatment Paradigm vs. Daily Topiramate | 1.35 Migraine attacks | Standard Deviation 1.31 |
| Frovatriptan | Number of Migraine Attacks in Participants Using Frovatriptan in a Preemptive Treatment Paradigm vs. Daily Topiramate | 2.12 Migraine attacks | Standard Deviation 1.75 |
Secondary
Adverse Events Associated With Study Medications
Includes Adverse Events at or above 5% frequency per group.
Time frame: Treatment Months 1 and 2
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Topiramate | Adverse Events Associated With Study Medications | 26 Adverse Events |
| Frovatriptan | Adverse Events Associated With Study Medications | 11 Adverse Events |
Secondary
Cost of Frovatriptan vs. Topiramate as Preventive Treatment of Migraine
Average cost of study medication taken by each subject. Measured in dollars.
Time frame: Treatment Months 1 and 2
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Topiramate | Cost of Frovatriptan vs. Topiramate as Preventive Treatment of Migraine | Preventive Medication Taken | 343.56 Dollars (US) | Standard Deviation 50.4774 |
| Topiramate | Cost of Frovatriptan vs. Topiramate as Preventive Treatment of Migraine | Rescue Medication Taken | 38.33 Dollars (US) | Standard Deviation 10.45 |
| Topiramate | Cost of Frovatriptan vs. Topiramate as Preventive Treatment of Migraine | All Study Medication Taken | 381.89 Dollars (US) | Standard Deviation 51.8816 |
| Frovatriptan | Cost of Frovatriptan vs. Topiramate as Preventive Treatment of Migraine | Preventive Medication Taken | 101.41 Dollars (US) | Standard Deviation 10.304 |
| Frovatriptan | Cost of Frovatriptan vs. Topiramate as Preventive Treatment of Migraine | Rescue Medication Taken | 59.94 Dollars (US) | Standard Deviation 9.54 |
| Frovatriptan | Cost of Frovatriptan vs. Topiramate as Preventive Treatment of Migraine | All Study Medication Taken | 161.35 Dollars (US) | Standard Deviation 70.1844 |
Secondary
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
Time frame: 2 Months
Population: Number of Units Analyzed is equivalent to number of headache days reported during Treatment Months 1 and 2.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Topiramate | Number of Headache Days Each Month Following Initiation of Treatment With Study Medication | Treatment Month 2 | 1.75 Headache Days | Standard Deviation 1.86 |
| Topiramate | Number of Headache Days Each Month Following Initiation of Treatment With Study Medication | Treatment Month 1 | 4.20 Headache Days | Standard Deviation 2.88 |
| Frovatriptan | Number of Headache Days Each Month Following Initiation of Treatment With Study Medication | Treatment Month 1 | 3.96 Headache Days | Standard Deviation 2.84 |
| Frovatriptan | Number of Headache Days Each Month Following Initiation of Treatment With Study Medication | Treatment Month 2 | 3.42 Headache Days | Standard Deviation 2.98 |
Secondary
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.
Time frame: Treatment Month 2
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Topiramate | Participant Satisfaction With Study Medications | Efficacy | 76.7857 Score on a Scale | Standard Deviation 21.04 |
| Topiramate | Participant Satisfaction With Study Medications | Functionality | 77.8214 Score on a Scale | Standard Deviation 22.68 |
| Topiramate | Participant Satisfaction With Study Medications | Ease of Use | 91.6607 Score on a Scale | Standard Deviation 11.5639 |
| Topiramate | Participant Satisfaction With Study Medications | Cost | 81.2536 Score on a Scale | Standard Deviation 19.85 |
| Topiramate | Participant Satisfaction With Study Medications | Bothersomeness of Side Effects | 95.1786 Score on a Scale | Standard Deviation 6.08 |
| Topiramate | Participant Satisfaction With Study Medications | Total Score | 82.0925 Score on a Scale | Standard Deviation 15.77 |
| Frovatriptan | Participant Satisfaction With Study Medications | Bothersomeness of Side Effects | 95.5398 Score on a Scale | Standard Deviation 6.81 |
| Frovatriptan | Participant Satisfaction With Study Medications | Efficacy | 75.1977 Score on a Scale | Standard Deviation 30.21 |
| Frovatriptan | Participant Satisfaction With Study Medications | Cost | 59.0886 Score on a Scale | Standard Deviation 32.86 |
| Frovatriptan | Participant Satisfaction With Study Medications | Functionality | 76.3648 Score on a Scale | Standard Deviation 29.98 |
| Frovatriptan | Participant Satisfaction With Study Medications | Total Score | 81.1417 Score on a Scale | Standard Deviation 21.76 |
| Frovatriptan | Participant Satisfaction With Study Medications | Ease of Use | 92.6989 Score on a Scale | Standard Deviation 11.36 |
Secondary
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
Time frame: 2 Months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Topiramate | Participants With Greater Than 50% Reduction in Migraine Attacks and Headache Days Per Month Utilizing Each Treatment Paradigm | Migraine Attacks Treatment Month 1 | 11 Participants |
| Topiramate | Participants With Greater Than 50% Reduction in Migraine Attacks and Headache Days Per Month Utilizing Each Treatment Paradigm | Headache Days Treatment Month 1 | 7 Participants |
| Topiramate | Participants With Greater Than 50% Reduction in Migraine Attacks and Headache Days Per Month Utilizing Each Treatment Paradigm | Migraine Attacks Treatment Month 2 | 15 Participants |
| Topiramate | Participants With Greater Than 50% Reduction in Migraine Attacks and Headache Days Per Month Utilizing Each Treatment Paradigm | Headache Days Treatment Month 2 | 16 Participants |
| Frovatriptan | Participants With Greater Than 50% Reduction in Migraine Attacks and Headache Days Per Month Utilizing Each Treatment Paradigm | Headache Days Treatment Month 2 | 13 Participants |
| Frovatriptan | Participants With Greater Than 50% Reduction in Migraine Attacks and Headache Days Per Month Utilizing Each Treatment Paradigm | Migraine Attacks Treatment Month 1 | 13 Participants |
| Frovatriptan | Participants With Greater Than 50% Reduction in Migraine Attacks and Headache Days Per Month Utilizing Each Treatment Paradigm | Migraine Attacks Treatment Month 2 | 15 Participants |
| Frovatriptan | Participants With Greater Than 50% Reduction in Migraine Attacks and Headache Days Per Month Utilizing Each Treatment Paradigm | Headache Days Treatment Month 1 | 9 Participants |
Secondary
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.
Time frame: Randomization, End of Treatment Month 1, End of Treatment Month 2
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Topiramate | Quality of Life in Subjects Utilizing Each Treatment Paradigm | Role Function Restrictive - Treatment Month 1 | 80.29 Score on a Scale | Standard Deviation 19.33 |
| Topiramate | Quality of Life in Subjects Utilizing Each Treatment Paradigm | Role Function Preventive - Treatment Month 2 | 93.95 Score on a Scale | Standard Deviation 7.57 |
| Topiramate | Quality of Life in Subjects Utilizing Each Treatment Paradigm | Role Function Preventive - Baseline | 77.75 Score on a Scale | Standard Deviation 16.02 |
| Topiramate | Quality of Life in Subjects Utilizing Each Treatment Paradigm | Emotional Function - Baseline | 60.67 Score on a Scale | Standard Deviation 22.47 |
| Topiramate | Quality of Life in Subjects Utilizing Each Treatment Paradigm | Role Function Restrictive - Treatment Month 2 | 86.64 Score on a Scale | Standard Deviation 13.98 |
| Topiramate | Quality of Life in Subjects Utilizing Each Treatment Paradigm | Emotional Function - Treatment Month 1 | 80.00 Score on a Scale | Standard Deviation 25.68 |
| Topiramate | Quality of Life in Subjects Utilizing Each Treatment Paradigm | Role Function Preventive - Treatment Month 1 | 85.25 Score on a Scale | Standard Deviation 18.32 |
| Topiramate | Quality of Life in Subjects Utilizing Each Treatment Paradigm | Emotional Function - Treatment Month 2 | 91.46 Score on a Scale | Standard Deviation 10.49 |
| Topiramate | Quality of Life in Subjects Utilizing Each Treatment Paradigm | Role Function Restrictive - Baseline | 56.00 Score on a Scale | Standard Deviation 15.88 |
| Frovatriptan | Quality of Life in Subjects Utilizing Each Treatment Paradigm | Emotional Function - Treatment Month 2 | 75.10 Score on a Scale | Standard Deviation 24.04 |
| Frovatriptan | Quality of Life in Subjects Utilizing Each Treatment Paradigm | Role Function Restrictive - Baseline | 59.88 Score on a Scale | Standard Deviation 16.65 |
| Frovatriptan | Quality of Life in Subjects Utilizing Each Treatment Paradigm | Role Function Restrictive - Treatment Month 1 | 66.48 Score on a Scale | Standard Deviation 18.75 |
| Frovatriptan | Quality of Life in Subjects Utilizing Each Treatment Paradigm | Role Function Restrictive - Treatment Month 2 | 71.84 Score on a Scale | Standard Deviation 19.57 |
| Frovatriptan | Quality of Life in Subjects Utilizing Each Treatment Paradigm | Role Function Preventive - Baseline | 77.50 Score on a Scale | Standard Deviation 18.53 |
| Frovatriptan | Quality of Life in Subjects Utilizing Each Treatment Paradigm | Role Function Preventive - Treatment Month 1 | 79.25 Score on a Scale | Standard Deviation 21.96 |
| Frovatriptan | Quality of Life in Subjects Utilizing Each Treatment Paradigm | Role Function Preventive - Treatment Month 2 | 84.96 Score on a Scale | Standard Deviation 16.67 |
| Frovatriptan | Quality of Life in Subjects Utilizing Each Treatment Paradigm | Emotional Function - Baseline | 64.71 Score on a Scale | Standard Deviation 23.13 |
| Frovatriptan | Quality of Life in Subjects Utilizing Each Treatment Paradigm | Emotional Function - Treatment Month 1 | 73.18 Score on a Scale | Standard Deviation 21.59 |