title: A double-blind, randomized, placebo-controlled, single-dose study of the cyclooxygenase-2 inhibitor, GW406381, as a treatment for acute migraine.
abstract: The objective of the present study was to explore the clinical efficacy and tolerability of GW406381, a cyclooxygenase-2 (COX-2) inhibitor with relatively high CNS penetration, in acute migraine. This was a double-blind, single-dose study of GW406381 compared with placebo and naproxen sodium compared with placebo (protocol number CXA20008). Three hundred and thirty-seven subjects were randomized 1:1:1 to GW406381 (70 mg), naproxen sodium (825 mg), or placebo for the treatment of one migraine headache of moderate or severe intensity in a potential 8-week period. The primary end-point was the proportion of subjects with headache relief [reduction in headache severity score from pre-dose 2 (moderate) or 3 (severe) to 0 (no pain) or 1 (mild)] at 2 h post-dose for GW406381 compared with placebo. Significantly higher proportions of subjects treated with GW406381 (50%, P = 0.032) or naproxen sodium (56%, P = 0.005) than with placebo (35%) reported headache relief at 2 h post-dose. Additional significant benefits were observed on many secondary outcomes, including proportions of subjects pain-free, for both GW406381 and naproxen sodium treatment compared with placebo. Both active treatments were well tolerated. Single-dose GW406381 (70 mg) and naproxen sodium (825 mg) were effective and well tolerated in the treatment of acute migraine.
authors.affiliation: Migraine Clinical Development, Neurosciences Medicines Development Center, GlaxoSmithKline, NC, USA. alison.l.wentz@gsk.com
authors.forename: A L
authors.initials: AL
authors.lastname: Wentz
authors.forename: T B
authors.initials: TB
authors.lastname: Jimenez
authors.forename: R M
authors.initials: RM
authors.lastname: Dixon
authors.forename: S K
authors.initials: SK
authors.lastname: Aurora
authors.forename: M
authors.initials: M
authors.lastname: Gold
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use*; D004311:Double-Blind Method; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D006841:Hydrocarbons, Aromatic / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D008881:Migraine Disorders / Q000188:drug therapy*; D009288:Naproxen / Q000627:therapeutic use; D009584:Nitrogen / Q000627:therapeutic use; D010147:Pain Measurement; D011720:Pyrazoles; D011724:Pyridazines; D018709:Statistics, Nonparametric; D013997:Time Factors
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; C469818:GW406381X; D006841:Hydrocarbons, Aromatic; D011720:Pyrazoles; D011724:Pyridazines; D009288:Naproxen; D009584:Nitrogen