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

This study has been completed.
Vernalis (R&D) Ltd
Information provided by:
Endo Pharmaceuticals
ClinicalTrials.gov Identifier:
First received: March 24, 2008
Last updated: June 13, 2011
Last verified: June 2011

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.

Condition Intervention Phase
Menstrually Associated Migraine
Drug: Frovatriptan
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double-Blind
Primary Purpose: Prevention

Resource links provided by NLM:

Further study details as provided by Endo Pharmaceuticals:

Primary Outcome Measures:
  • Incidence of menstrually associated migraine (MAM) headache in the treated peri-menstrual period (PMP) [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Incidence of moderate or severe MAM headaches [ Designated as safety issue: No ]
  • Incidence of severe MAM headaches [ Designated as safety issue: No ]
  • Duration of MAM headaches [ Designated as safety issue: No ]
  • Maximum headache intensity [ Designated as safety issue: No ]
  • Incidence of MAM headache associated symptoms and characteristics [ Designated as safety issue: No ]
  • Duration of MAM headache associated symptoms [ Designated as safety issue: No ]
  • Maximum functional impairment score during MAM headache [ Designated as safety issue: No ]
  • Incidence of moderate or severe functional impairment during MAM headache [ Designated as safety issue: No ]
  • Duration of moderate or severe functional impairment during MAM headache [ Designated as safety issue: No ]
  • Incidence of use of rescue medication for the treatment of a MAM headache [ Designated as safety issue: No ]
  • Patient satisfaction score at the end of each 6 day treated PMP [ Designated as safety issue: No ]
  • Adverse events [ Designated as safety issue: Yes ]
  • Standard hematology and biochemistry [ Designated as safety issue: Yes ]
  • 12-lead ECGs, physical exam, vital signs [ Designated as safety issue: Yes ]

Enrollment: 579
Study Start Date: June 2001
Study Completion Date: June 2002
Primary Completion Date: June 2002 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1 Drug: Frovatriptan
2.5 mg tablet administered once daily for 6 days starting 2 days before the anticipated onset of a MAM headache
Active Comparator: 2 Drug: Frovatriptan
2.5 mg tablet administered twice daily for 6 days, starting 2 days before the anticipated onset of a MAM headache.
Placebo Comparator: 3 Drug: Placebo
placebo tablet administered for 6 days, starting 2 days before the anticipated onset of a MAM headache.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No

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
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00644033

United States, Pennsylvania
Endo Pharmaceuticals
Chadds Ford, Pennsylvania, United States, 19317
Sponsors and Collaborators
Endo Pharmaceuticals
Vernalis (R&D) Ltd
Principal Investigator: Arthur Elkind, MD Elkind Headache Center
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: John C. Campbell, Director, Medical Affairs, Endo Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00644033     History of Changes
Other Study ID Numbers: VML 251 00/02 
Study First Received: March 24, 2008
Last Updated: June 13, 2011
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Physiological Effects of Drugs
Serotonin Agents
Serotonin Receptor Agonists

ClinicalTrials.gov processed this record on May 23, 2016