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

Elias Packman, Rina Leyva, David Kellstein, Elias Packman, Rina Leyva, David Kellstein

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: This novel ibuprofen sodium tablet provided rapid, efficacious relief of ETTH and was well tolerated.

Trial registration: ClinicalTrials.gov NCT01362491.

Keywords: Analgesia; Fast-absorbed ibuprofen; Ibuprofen sodium; Over the counter; Tension headache.

Figures

Figure 1
Figure 1
Subject disposition. IBUMot, Motrin®; IBUNa, ibuprofen sodium dihydrate; ITT, intent-to-treat.
Figure 2
Figure 2
Two- and 3-hour summary efficacy measures. *P ≤ .001 vs placebo; IBUMot, Motrin®; IBUNa, ibuprofen sodium dihydrate; SE, standard error; SPID, sum of pain intensity difference scores; SPRID, time-weighted sum of Pain Relief Rating and pain intensity difference scores; TOTPAR, time-weighted sum of Pain Relief Rating scores; 0–3, from time 0 to 3 hours after study administration; 0–2, from time 0 to 2 hours after study administration.
Figure 3
Figure 3
Time to meaningful pain relief (hour 0–1). *P < .001 vs placebo; IBUMot, Motrin®; IBUNa, ibuprofen sodium dihydrate; MPR, meaningful pain relief.
Figure 4
Figure 4
Time to first perceptible pain relief (hour 0–1). *P < .001 vs placebo; FPR, first perceptible relief; IBUMot, Motrin®; IBUNa, ibuprofen sodium dihydrate.
Figure 5
Figure 5
Sum of pain relief rating and pain intensity difference (PRID) scores over time. *IBUNa and IBUMot both P < .001 vs placebo; IBUMot, Motrin®; IBUNa, ibuprofen sodium dihydrate.

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