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.

Meta‐Analysis of the Efficacy and Safety of Naproxen Sodium in the Acute Treatment of Migraine

“…Study Characteristics.— Figure 1 summarizes the process of identifying eligible studies. We identified 16 published papers 6‐9,15‐26 reporting the result of 17 randomized controlled trials of naproxen in the treatment of migraine. All were published in English.…”

“…One study each assessed outcomes at monthly interval, 6 evaluated a tablet of combined sumatriptan and naproxen sodium against placebo, 24 reported severity, duration, and frequency of head pain, 7 and function, productivity, and satisfaction outcomes 25 . The remaining 3 papers involving the result of 4 trials met our inclusion criteria for meta‐analysis 8,9,26 . It was noted that one 9 of the included papers reported the results from 2 trials and therefore was treated as 2 separate studies.…”

“…It was noted that one 9 of the included papers reported the results from 2 trials and therefore was treated as 2 separate studies. Doses of naproxen sodium used were 500 mg 8,9 and 825 mg 26 . Characteristics of the included trials are presented in the Table.…”

“…Headache Relief.— A total of 2168 patients enrolled in the 4 trials of naproxen sodium that reported the results in terms of the proportion of patients whose pain intensity reduced from severe or moderate to mild or none within 2 and 4 hours after treatment 8,9,26 . As expected, naproxen sodium was more effective than placebo in achieving headache relief.…”

Neurology in the European Journal of Neurology

“…Perhaps it is not surprising therefore that we see a substantial majority of articles on stroke [1–78], multiple sclerosis [Refs 79–130], Parkinson’s disease [131–183] and other movement disorders [184–209] and the dementias [210–244]. However, other areas such as motor neuron disease/amyotrophic lateral sclerosis [245–259], headache [260–282], epilepsy [283–290], myasthenia gravis [291–297] and spinal diseases [298–304] also figure strongly. Interestingly, we are publishing an increasing proportion of papers on the genetics of neurological disorders, as shown in these lists.…”