A Randomized Trial of Frovatriptan for the Intermittent Prevention of Menstrual Migraine

Study Overview
=================
Brief Summary
-----------------
The primary objective of this study was to determine whether frovatriptan was effective in the prevention of menstrually associated migraine (MAM) headaches when compared to placebo. Secondary objectives included determining the effectiveness of frovatriptan in reducing the incidence, severity and duration of MAM headaches and associated symptoms, to evaluate the safety and tolerability of the two frovatriptan dosing regimens and to compare the effectiveness of these regimens in the prevention of MAM headaches. In this cross-over study, patients treated each of 3 perimenstrual periods (PMPs) with placebo, frovatriptan 2.5 mg daily (QD) and 2.5 mg twice daily (BID) for 6 days, starting 2 days before the anticipated onset of a MAM headache. A statistically significant reduction in the incidence of MAM headache (p<0.0001) was observed with both dosing regimens of frovatriptan when compared to placebo. Additionally, the frovatriptan BID regimen was superior to the frovatriptan QD regimen in the prevention of MAM headache (p<0.001). Significant reductions in MAM headache severity and duration, the incidence of associated symptoms and characteristics, and the use of rescue medication were observed when the PMP was treated with frovatriptan, compared to placebo. Both dose regimens of frovatriptan were equally well tolerated and no cardiovascular or other safety and tolerability concerns arose with repeated administration of frovatriptan over a 6 day period.

Conditions
-----------------
Menstrually Associated Migraine

Intervention / Treatment
-----------------
* Drug: Frovatriptan
* Drug: Frovatriptan
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Females aged 18 years and over 12 month or more documented history of menstrual migraine headache, according to International Headache Society classification An average frequency of MAM attacks in at lease 3 out of 4 menstrual cycles Regular predictable menstrual periods Able to accurately predict the onset of MAM headaches occurring between Day -2 and Day +4 of menses Able and willing to sign informed consent to comply with study procedures, including completion of diary cards Exclusion Criteria: More than three migraine attacks per month that were not MAM attacks Coronary artery disease including coronary vasospasm Significant cerebrovascular disease including basilar or hemiplegic migraine Uncontrolled hypertension Severe hepatic or renal insufficiency More than 15 headache days per month Any other condition or serious illness which would interfere with optimal participation in the study History of clinically relevant allergy, including that to frovatriptan or other triptans Pregnant or breast feeding or intending to become pregnant or to breast-feed during study period Participated in other frovatriptan menstrual migraine prevention studies Use of another investigation drug within 30 days or 5 half-lives (whichever is longer) before the screening visit

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br> | Drug: Frovatriptan<br>* 2.5 mg tablet administered once daily for 6 days starting 2 days before the anticipated onset of a MAM headache<br>|
| Active Comparator: 2<br> | Drug: Frovatriptan<br>* 2.5 mg tablet administered twice daily for 6 days, starting 2 days before the anticipated onset of a MAM headache.<br>|
| Placebo Comparator: 3<br> | Drug: Placebo<br>* placebo tablet administered for 6 days, starting 2 days before the anticipated onset of a MAM headache.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of menstrually associated migraine (MAM) headache in the treated peri-menstrual period (PMP) |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of moderate or severe MAM headaches |  |  | 
| Incidence of severe MAM headaches |  |  | 
| Duration of MAM headaches |  |  | 
| Maximum headache intensity |  |  | 
| Incidence of MAM headache associated symptoms and characteristics |  |  | 
| Duration of MAM headache associated symptoms |  |  | 
| Maximum functional impairment score during MAM headache |  |  | 
| Incidence of moderate or severe functional impairment during MAM headache |  |  | 
| Duration of moderate or severe functional impairment during MAM headache |  |  | 
| Incidence of use of rescue medication for the treatment of a MAM headache |  |  | 
| Patient satisfaction score at the end of each 6 day treated PMP |  |  | 
| Adverse events |  |  | 
| Standard hematology and biochemistry |  |  | 
| 12-lead ECGs, physical exam, vital signs |  |  |