A phase II, randomized, double-blind, crossover study was designed to evaluate the efficacy of 100-mg
diclofenac sodium softgel (formulated using ProSorb technology) with or without 100-mg
caffeine versus placebo in migraineurs during
migraine attacks.
BACKGROUND: METHODS: The 3-period crossover study was designed to compare
diclofenac softgel 100 mg,
diclofenac softgel 100 mg plus
caffeine 100 mg, and placebo in the acute treatment of
migraine. Subjects treated one moderate or severe attack with each study medication. The primary efficacy parameter was the percentage of subjects with
headache relief at 60 minutes as defined by a reduction of
headache severity from moderate or severe at baseline to absent or mild compared with placebo. Though the sample size estimate required that 72 subjects treat 3 separate attacks, 51 subjects treated 1
migraine attack, 44 treated 2 attacks, and 39 treated 3 attacks. Results.-In the placebo group, 6 (14%) of 43 subjects reported
headache relief at 60 minutes versus 12 (27%) of 45 subjects in the
diclofenac softgel group, and 19 (41%) of 46 subjects in the
diclofenac softgel plus
caffeine group. Differences were statistically significant for the
diclofenac softgel plus
caffeine group versus placebo (odds ratio, 4.2; 95% confidence interval, 1.3 to 13.7). Rescue medication was used by 27 (63%) of 43 subjects treated with placebo, 15 (33%) of 45 subjects treated with
diclofenac softgel, and 14 (30%) of 46 subjects treated with
diclofenac softgel plus
caffeine. This result is highly statistically significant (chi22= 11.56, P=.003). Both the
diclofenac plus
caffeine (P <.03) and
diclofenac only (P <.03) groups were significantly different from the placebo group in terms of the visual analog scale score at 60 minutes.
CONCLUSIONS: The major finding of the present study is that
diclofenac softgel plus
caffeine produces statistically significant benefits relative to placebo at 60 minutes.
Diclofenac softgel alone did not differ significantly from placebo, perhaps due to limits in sample size. Nonsignificant trends support the
analgesic adjuvant benefit of
caffeine when added to
diclofenac softgels.