Celecoxib in the treatment of primary dysmenorrhea: results from two randomized, double-blind, active- and placebo-controlled, crossover studies.
BACKGROUND
Celecoxib, a cyclooxygenase-2 inhibitor, has established analgesic efficacy for the treatment of acute pain resulting from a variety of causes.


OBJECTIVE
This article describes 2 studies designed to assess the efficacy and tolerability of celecoxib in patients with primary dysmenorrhea.


METHODS
Two identical, 3-day, multiple-dose, randomized, double-blind, active- and placebo-controlled, crossover studies were carried out in women aged 18 to 44 years with primary dysmenorrhea (studies 1 and 2). The studies employed a 6-sequence, 3-period, complete-block crossover design over 3 menstrual cycles. Patients received celecoxib 400 mg, followed by celecoxib 200 mg no sooner than 12 hours after first dose (day 1), then celecoxib 200 mg q12h as necessary (days 2 and 3); naproxen sodium 550 mg followed by naproxen sodium 550 mg no sooner than 12 hours after first dose (day 1), then naproxen sodium 550 mg q12h as necessary (days 2 and 3); or placebo. Primary efficacy measures were time-weighted sum of total pain relief and time-weighted sum of pain intensity difference at 8 hours after administration of the first dose of study medication (TOTPAR[8] and SPID[8], respectively). Tolerability was assessed using routine physical examination, including vital sign measurements, and clinical laboratory analyses at screening and end of study.


RESULTS
In total, 149 and 154 patients were randomized to 1 of the 6 treatment sequences in studies 1 and 2, respectively. Across treatment sequences, mean age ranges were 23.4 to 26.9 years (study 1) and 28.3 to 34.1 years (study 2). Mean weight ranges were 62.7 to 74.5 kg (study 1) and 69.2 to 86.7 kg (study 2). Most patients (96.6% in study 1, 80.5% in study 2) were white. Mean TOTPAR[8] values with celecoxib (study 1/study 2, 18.28/17.98) and naproxen sodium (20.59/21.27) were significantly greater than with placebo (12.82/12.98) (all, P < 0.001). Mean SPID[8] values were significantly greater with celecoxib (10.06/9.60) and naproxen sodium (11.48/11.71) than with placebo (5.96/6.41) (all, P < 0.001). Naproxen sodium was significantly different from celecoxib in TOTPAR[8] (study 2 only) and SPID[8] (both studies) (all, P < 0.001). In both studies, the adverse-events (AEs) profile was not significantly different between treatments, with the majority of AEs being related to primary dysmenorrhea and not medication. Less than 10% of patients experienced severe AEs in any treatment period.


CONCLUSIONS
In these 2 identically designed studies in women aged 18 to 44 years, celecoxib 400 mg (followed by 200 mg q12h) was more effective, as measured using pain scores, in the treatment of primary dysmenorrhea compared with placebo. In each study, the primary efficacy measures-TOTPAR[8] and SPID[8] scores-were significantly improved with celecoxib and naproxen sodium compared with placebo. SPID[8] in both studies and TOTPAR[8] in study 2 were significantly improved with naproxen sodium compared with celecoxib. Both celecoxib and naproxen sodium were well tolerated and provided relief from menstrual pain within 1 hour of administration.
Daniels
Stephen
S
ClinicaI Research Centers-Premier Research Group Ltd. (formerly Scirex Clinical Research Centers), Austin, Texas 78705, USA. stephen.daniels@premier-research.com
Robbins
Jeffery
J
West
Christine R
CR
Nemeth
Mary Anne
MA
D000293:Adolescent; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000068579:Celecoxib; D018592:Cross-Over Studies; D051546:Cyclooxygenase 2 / Q000187:drug effects / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004412:Dysmenorrhea / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D009288:Naproxen / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D010147:Pain Measurement; D011720:Pyrazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D055815:Young Adult
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D009288:Naproxen; D051546:Cyclooxygenase 2; D000068579:Celecoxib