title: Comparison of frovatriptan plus dexketoprofen (25 mg or 37.5 mg) with frovatriptan alone in the treatment of migraine attacks with or without aura: a randomized study.
abstract: BACKGROUND
  Drugs for migraine attacks include triptans and NSAIDs; their combination could provide greater symptom relief.
  
  
  METHODS
  A total of 314 subjects with history of migraine, with or without aura, were randomized to frovatriptan 2.5 mg alone (Frova), frovatriptan 2.5 mg + dexketoprofen 25 mg (FroDex25) or frovatriptan 2.5 mg + dexketoprofen 37.5 mg (FroDex37.5) and treated at least one migraine attack. This was a multicenter, randomized, double-blind, parallel-group study. The primary end point was the proportion of pain free (PF) at two hours. Secondary end points were PF at one and four hours, pain relief (PR) at one, two, four hours, sustained PF (SPF) at 24 and 48 hours, recurrence at 48 hours, resolution of nausea, photophobia and phonophobia at two and four hours, the use of rescue medication and the judgment of the treatment.
  
  
  RESULTS
  The results were assessed in the full analysis set (FAS) population, which included all subjects randomized and treated for whom at least one post-dose intensity of headache was recorded. The proportions of subjects PF at two hours (primary end point) were 29% (27/93) with Frova compared with 51% (48/95 FroDex25 and 46/91 FroDex37.5) with each combination therapies ( P < 0.05). Proportions of SPF at 24 hours were 24% (22/93) for Frova, 43% (41/95) for FroDex25 ( P < 0.001) and 42% (38/91) for FroDex37.5 ( P < 0.05). SPF at 48 hours was 23% (21/93) with Frova, 36% (34/95) with FroDex25 and 33% (30/91) with FroDex37.5 ( P = NS). Recurrence was similar for Frova (22%, 6/27), FroDex25 (29%, 14/48) and FroDex37.5 (28%, 13/46) ( P = NS), meaning a lack of improvement with the combination therapy. Statistical adjustment for multiple comparisons was not performed. No statistically significant differences were reported in the occurrence of total and drug-related adverse events. FroDex25 and FroDex37.5 showed a similar efficacy both for primary and secondary end points. There did not seem to be a dose response curve for the addition of dexketoprofen.
  
  
  CONCLUSIONS
  FroDex improved initial efficacy at two hours compared to Frova whilst maintaining efficacy at 48 hours in this study. Tolerability profiles were comparable. Intrinsic pharmacokinetic properties of the two single drugs contribute to this improved efficacy profile.
authors.affiliation: Department of Clinical Neuroscience, National Neurological Institute Carlo Besta, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Tullo
authors.forename: Fabio
authors.initials: F
authors.lastname: Valguarnera
authors.forename: Piero
authors.initials: P
authors.lastname: Barbanti
authors.forename: Pietro
authors.initials: P
authors.lastname: Cortelli
authors.forename: Giuliano
authors.initials: G
authors.lastname: Sette
authors.forename: Gianni
authors.initials: G
authors.lastname: Allais
authors.forename: Florindo
authors.initials: F
authors.lastname: d'Onofrio
authors.forename: Marcella
authors.initials: M
authors.lastname: Curone
authors.forename: Dario
authors.initials: D
authors.lastname: Zava
authors.forename: Deborha
authors.initials: D
authors.lastname: Pezzola
authors.forename: Chiara
authors.initials: C
authors.lastname: Benedetto
authors.forename: Fabio
authors.initials: F
authors.lastname: Frediani
authors.forename: Gennaro
authors.initials: G
authors.lastname: Bussone
mesh_terms: D000328:Adult; D000700:Analgesics / Q000008:administration & dosage*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage; D002227:Carbazoles / Q000008:administration & dosage*; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007660:Ketoprofen / Q000008:administration & dosage / Q000031:analogs & derivatives*; D008297:Male; D008875:Middle Aged; D008881:Migraine Disorders / Q000188:drug therapy*; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage; D014325:Tromethamine / Q000008:administration & dosage*; D014363:Tryptamines / Q000008:administration & dosage*
chemical_list: D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D002227:Carbazoles; D004338:Drug Combinations; D017366:Serotonin Receptor Agonists; D014363:Tryptamines; D014325:Tromethamine; D007660:Ketoprofen; C108128:frovatriptan; C118296:dexketoprofen trometamol
keywords: Frovatriptan; NSAIDs; dexketoprofen; migraine attacks; triptans