Onset of analgesia with ibuprofen sodium in tension-type headache: a randomized trial

Elias Packman, Rina Leyva, David Kellstein

Ibuprofen is known to be efficacious in the treatment of tension-type headache, the most common form of primary headache. A novel tablet formulation of ibuprofen sodium is more rapidly absorbed than standard ibuprofen. This study evaluated onset of analgesia and overall efficacy of ibuprofen sodium in episodic-type tension headache (ETTH) compared with standard ibuprofen and placebo. This randomized, double-blind, single-center, parallel-group study included adults aged 18-65 years with ≥4 moderately severe ETTHs per month for 6 months. Within 45 minutes of onset of at least moderately severe ETTH, subjects were randomized 2:2:1 to receive a single oral dose of ibuprofen sodium tablets (Advil® Film Coated; 2 × 256 mg [equivalent to 400 mg standard ibuprofen]), standard ibuprofen tablets (Motrin®; 2 × 200 mg), or placebo. The coprimary end points were time-weighted sum of pain relief rating and pain intensity difference scores over 3 hours (SPRID 0-3) and time to meaningful pain relief (MPR) assessed by double-stopwatch method. A total of 226 subjects were randomized to ibuprofen sodium (n = 91), standard ibuprofen (n = 89), and placebo (n = 46). Demographics and baseline characteristics were comparable between treatment groups. Mean SPRID 0-3 scores were significantly superior (P < .001) for ibuprofen sodium (9.6) and standard ibuprofen (9.8) versus placebo (3.5), but were not significantly different from each other (P = .812). Time to MPR was significantly (P < .001) shorter for ibuprofen sodium and standard ibuprofen compared with placebo (median 40.6, 48.5, and >180 minutes, respectively). Time to MPR was numerically faster for ibuprofen sodium than standard ibuprofen. This difference was not statistically significant (P = .253) using the protocol-specified analysis but was (P = .022) in a post hoc analysis using the Gehan-Wilcoxon test, which assigns higher weights to earlier events. (The post hoc analysis was performed because Kaplan-Meier graphs and results for time to first perceptible relief favored ibuprofen sodium over standard ibuprofen at earlier time points.) There were no adverse events. This novel ibuprofen sodium tablet provided rapid, efficacious relief of ETTH and was well tolerated. ClinicalTrials.gov NCT01362491.