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

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.

OBJECTIVE

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 ( approximately 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<0.001), and on all secondary end points (P<0.05, comparisons of all CS-706 doses vs placebo) with the exception of time to 100% PR for CS-706 10 mg. Single 50-, 100-, and 200-mg doses of CS-706 also were significantly more effective than celecoxib for TOPAR4 (P=0.036, P=0.004, and P=0.006, respectively). The onset of analgesia (PID >or= 1) for all CS-706 doses occurred within 1 hour after dosing (P<0.001 vs placebo). The median duration of analgesia, measured as the time to administration of rescue medication, was significantly greater for all doses of CS-706 compared with placebo (5.7 hours for CS-706 10 mg, >24 hours for CS-706 50, 100, and 200 mg, and 1.7 hours for placebo; P<0.001 for CS-706 50, 100, and 200 mg). These data suggest that once-daily administration of CS-706 may be effective in providing relief of acute pain. The incidence of adverse events was similar among all treatment groups. Adverse events occurring in >or= 5 % of subjects in any treatment group were nausea, vomiting, dry socket, dizziness, headache, and paresthesia.

CONCLUSIONS

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.