Dose-ranging analgesic study of ProSorb®* diclofenac potassium in postsurgical dental pain

Background: ProSorb(R) diclofenac potassium (K) is a novel, liquid-filled, rapid-dispersion formulation of the nonsteroidal anti-inflammatory drug diclofenac, placed into soft gelatin capsules. Its time to maximal plasma drug concentration has been shown to be approximately half, and its maximal plasma drug concentration nearly twice, that of immediate-release diclofenac K tablets. Objective: This study compared the analgesic dose-response relationship and tolerability of 3 doses of ProSorb diclofenac K and placebo in the treatment of pain after dental impaction surgery. Methods: This randomized, double-blind, double-dummy, placebo-controlled, parallel-group study was conducted at 6 centers across the United States. Patients aged 18 to 65 years with moderate or severe pain after the removal of greater than or equal to1 impacted mandibular third molar were randomly assigned to receive a single dose of ProSorb diclofenac K 25, 50, or 100 mg or placebo. Pain intensity and relief were assessed up to 6 hours after dosing. Rescue treatment was allowed after 1 hour. Efficacy end points included the summed pain intensity difference over 3 and 6 hours (SPID3 and 6); total pain relief at 3 and 6 hours (TOTPAR3 and 6); median times to onset of perceptible and meaningful relief (analgesic onset) and rescue medication use (analgesic duration); and cumulative percentage of patients using rescue medication. Tolerability was assessed using vital sign measurements and spontaneous reporting of adverse events. Results: A total of 265 patients (154 women, 111 men; mean age, 23.3 years) were enrolled. All 3 ProSorb diclofenac K groups showed higher SPID6 and TOTPAR6 scores and longer median times to rescue medication use than the placebo group (all, P < 0.001). For these end points, a dose-response relationship was evident between the 100-mg dose and the 25- and 50-mg doses (P less than or equal to 0.05); the 25- and 50-mg doses were similar. In the diclofenac groups, median onset times for first perceptible (less than or equal to 22.5 min) and meaningful (less than or equal to 53.0 min) relief were significantly more rapid than placebo (P less than or equal to 0.01). Proportions of patients requiring rescue analgesic were less than or equal to50.8% with diclofenac compared with 79.4% with placebo. Proportions of patients assigning a global evaluation of good or better was greater than or equal to68% with diclofenac compared with 21% for placebo. Tolerability was similar across all treatment groups. Conclusion: In this study of patients treated for pain following dental impaction surgery, single doses of ProSorb diclofenac K 25, 50, and 100 mg were more efficacious than placebo with respect to reduction of pain. All 3 doses provided a rapid analgesic onset and were well tolerated. (Clin Ther. 2004 26:1215-1227) Copyright (C) 2004 Excerpta Medica, Inc.