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

• ClinicalTrials.gov Identifier: NCT00846495
• Recruitment Status: Completed
• First Posted: February 18, 2009
• Results First Posted: August 9, 2011
• Last Update Posted: January 13, 2012
• Sponsor: Clinvest
• Collaborator: Endo Pharmaceuticals
• Information provided by (Responsible Party): Clinvest, Cady, Roger, M.D.

Tracking Information

• First Submitted Date: February 17, 2009
• First Posted Date: February 18, 2009
• Results First Submitted Date: June 9, 2011
• Results First Posted Date: August 9, 2011
• Last Update Posted Date: January 13, 2012
• Study Start Date: August 2009
• Actual Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 12, 2011)

• Number of Migraine Attacks in Participants Using Frovatriptan in a Preemptive Treatment Paradigm vs. Daily Topiramate [ Time Frame: 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 [ Time Frame: 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

Original Primary Outcome Measures (submitted: February 17, 2009)

• To compare the number of migraine attacks in subjects using frovatriptan in a pre-emptive treatment paradigm vs. daily topiramate [ Time Frame: By Diary following 2-month Treatment Period ]
• To compare efficacy of frovatriptan used in a pre-emptive treatment paradigm vs. daily topiramate to prevent migraine [ Time Frame: Following 2-month Treatment Period ]

Current Secondary Outcome Measures (submitted: July 12, 2011)

• Number of Headache Days Each Month Following Initiation of Treatment With Study Medication [ Time Frame: 2 Months ]
  Measure the change in number of headache days reported by participants during each treatment month following initiation of treatment with study medication
• Participants With Greater Than 50% Reduction in Migraine Attacks and Headache Days Per Month Utilizing Each Treatment Paradigm [ Time Frame: 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
• Quality of Life in Subjects Utilizing Each Treatment Paradigm [ Time Frame: 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 [ Time Frame: 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.
• Adverse Events Associated With Study Medications [ Time Frame: Treatment Months 1 and 2 ]
  Includes Adverse Events at or above 5% frequency per group.
• Cost of Frovatriptan vs. Topiramate as Preventive Treatment of Migraine [ Time Frame: Treatment Months 1 and 2 ]
  Average cost of study medication taken by each subject. Measured in dollars.

Original Secondary Outcome Measures (submitted: February 17, 2009)

• To measure change in migraine frequency and number of headache days per month following initiation of treatment with study medication [ Time Frame: Following 2-month Treatment Period ]
• To identify subjects with greater than 50% reduction in migraine attacks and headache days per month utilizing each treatment paradigm [ Time Frame: Following 2-month Treatment Period ]
• To evaluate change in quality of life in subjects utilizing each treatment paradigm [ Time Frame: Following 2-month Treatment Period ]
• To measure subject satisfaction with study medications [ Time Frame: Following 2-month Treatment Period ]
• To evaluate adverse events associated with study medications [ Time Frame: Following 2-month Treatment Period ]
• To compare the projected cost of frovatriptan vs. topiramate as preventive treatment of migraine [ Time Frame: Following 2-month Treatment Period ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Pilot Study to Compare Frovatriptan vs. Topiramate for Prevention of Migraine
• Official Title: A Randomized, Single-Blind Pilot Study to Compare the Efficacy and Cost-Effectiveness of Frovatriptan vs. Topiramate for the Prevention of Migraine
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Investigator); Primary Purpose: Prevention
• Condition: Migraine

Intervention

• Drug: topiramate
  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
  Other Name: Topamax
• Drug: frovatriptan
  frovatriptan 5mg tab during premonitory phase of migraine
  Other Name: Frova

Study Arms

• Active Comparator: topiramate
  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.
  Intervention: Drug: topiramate
• Active Comparator: frovatriptan
  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).
  Intervention: Drug: frovatriptan

• Publications *: Luciani R, Carter D, Mannix L, Hemphill M, Diamond M, Cady R. Prevention of migraine during prodrome with naratriptan. Cephalalgia. 2000 Mar;20(2):122-6. doi: 10.1046/j.1468-2982.2000.00030.x.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 12, 2011): 55
• Original Estimated Enrollment (submitted: February 17, 2009): 60
• Actual Study Completion Date: January 2011
• Actual Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00846495
• Other Study ID Numbers: Frova vs. Topiramate
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Clinvest, Cady, Roger, M.D.
• Original Responsible Party: Roger K. Cady, MD, Clinvest
• Current Study Sponsor: Clinvest
• Original Study Sponsor: Cady, Roger, M.D.
• Collaborators: Endo Pharmaceuticals

Investigators

• Principal Investigator: Roger K Cady, MD; Clinvest

• PRS Account: Cady, Roger, M.D.
• Verification Date: January 2012