Dose range-finding studies with frovatriptan in the acute treatment of migraine.
OBJECTIVE
To determine the optimum dose of frovatriptan for the acute treatment of migraine.


BACKGROUND
Frovatriptan is a new triptan developed for the acute treatment of migraine. The dose-response characteristics and safety of frovatriptan have been investigated across a broad range of doses from 0.5 to 40 mg.


METHODS
Two randomized, placebo-controlled, double-blind, parallel-group trials, with a total of 1453 patients, were performed to determine the optimal dose of the 5-HT(B/1D)agonist, frovatriptan, for the acute treatment of migraine. The dose ranges studied were 2.5 to 40 mg in the high-dose study and 0.5 to 5 mg in the low-dose study.


RESULTS
At 2 hours postdosing for initial moderate or severe headache (International Headache Society grades 2 or 3), there was an approximate two-fold difference in the proportion of patients taking frovatriptan doses of 2.5 to 40 mg with mild or no headache compared to placebo. Frovatriptan doses of 0.5 mg and 1 mg were not more effective than placebo at 2 hours postdose, and 2.5 mg was identified as the lowest effective dose for the relief of migraine and accompanying symptoms. Above 2.5 mg, no dose-response relationship was observed for any efficacy parameters. There was an increase in the incidence of adverse events from 10 mg and above, but the vast majority were rated as mild in severity and did not impact upon tolerability in a significant manner.


CONCLUSIONS
Frovatriptan was well tolerated throughout the dose range of 0.5 to 40 mg. The 2.5-mg dose confers the optimal balance of efficacy and tolerability for the acute treatment of migraine.
Rapoport
Alan
A
The New England Center for Headache, Stamford, Conn 06902-1251, USA.
Ryan
Robert
R
Goldstein
Jerome
J
Keywood
Charlotte
C
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D002227:Carbazoles / Q000009:adverse effects / Q000627:therapeutic use*; D004244:Dizziness / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008881:Migraine Disorders / Q000188:drug therapy*; D009325:Nausea / Q000139:chemically induced; D012008:Recurrence; D017366:Serotonin Receptor Agonists / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014363:Tryptamines; D014481:United States
D002227:Carbazoles; D017366:Serotonin Receptor Agonists; D014363:Tryptamines; C108128:frovatriptan