Efficacy and Safety of Pelubiprofen for Primary Dysmenorrhea: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Two-Period Crossover Trial

Abstract

Background: Primary dysmenorrhea is a common gynecologic condition that frequently requires pharmacologic treatment. Pelubiprofen, a 2-arylpropionic acid-derived prodrug with relatively selective cyclooxygenase-2 inhibitory activity, has demonstrated analgesic efficacy in acute pain conditions. Methods: This multicenter, randomized, double-blind, placebo-controlled, crossover phase 3 trial randomized 120 women aged 19-44 years with primary dysmenorrhea to one of two treatment sequences over two menstrual cycles. Pelubiprofen at 45 mg or a matching placebo was administered at the onset of moderate or severe menstrual pain. The co-primary endpoints were time-weighted sums of the total pain relief (TOTPAR-8) and pain intensity difference (SPID-8) during the first 8 h after dosing. Results: Of 120 randomized women, 115 comprised the modified intention-to-treat population and 116 comprised the safety population. Pelubiprofen demonstrated significantly greater analgesic efficacy than placebo, with least-squares mean TOTPAR-8 values of 22.17 versus 15.50 and SPID-8 values of 10.00 versus 6.17 (both p < 0.0001). Significant between-treatment differences were also observed at 12 h (TOTPAR-12 and SPID-12). Treatment-emergent adverse events occurred in 9/113 (8.0%) pelubiprofen treatment periods and 10/112 (8.9%) placebo treatment periods; all events were mild to moderate, and the only serious adverse event occurred during a placebo treatment period and was judged to be unrelated to study treatment. Conclusions: Pelubiprofen at 45 mg provided superior short-term analgesic efficacy compared with placebo and was generally well tolerated in women with primary dysmenorrhea.