A randomized, double-blind, celecoxib- and placebo-controlled study of the effectiveness of CS-706 in acute postoperative dental pain

Abstract Background: CS-706 is a cyclooxygenase-2 (COX-2)-selective inhibitor with an in vitro selectivity ratio (COX-1:COX-2) similar to that of celecoxib. It has exhibited analgesic, anti-inflammatory, and antitumor properties in animal models. Objectives: This study evaluated the tolerability of single doses of CS-706 and compared the analgesic efficacy of CS-706 with that of celecoxib and placebo in the dental pain model. Methods: This was a randomized, double-blind, double-dummy, active- and placebo-controlled study. Healthy male and female subjects with moderate to severe pain intensity (PI) after dental surgery were randomized (∼50 per group) to receive a single oral dose of CS-706 10, 50, 100, or 200 mg; celecoxib 400 mg; or placebo. PI and pain relief (PR) were measured on categorical and visual analog scales through 24 hours after the dose. The primary efficacy variable was the time-weighted sum of PR scores at 4 hours after the dose (TOPAR4). The onset of analgesia was assessed by calculating the pain intensity difference (PID). Perceptible and meaningful pain relief were assessed using a 2-stopwatch method. Results: The majority of subjects were female (62.0%) and white (59.5%). Subjects' mean (SD) age was 22.6 (3.9) years, and their mean body mass index was 25.3 (5.1) kg/m 2 . All doses of CS-706 were associated with significant analgesic efficacy compared with placebo based on the primary end point, TOPAR4 ( P P P = 0.036, P = 0.004, and P = 0.006, respectively). The onset of analgesia (PID ≥ 1) for all CS-706 doses occurred within 1 hour after dosing ( P 24 hours for CS-706 50, 100, and 200 mg, and 1.7 hours for placebo; P Conclusion: Single doses of CS-706 had significant analgesic efficacy compared with celecoxib and placebo in the relief of postoperative dental pain in the healthy subjects enrolled in this study.