Indomethacin submicron particle capsules provide effective pain relief in patients with acute pain: a phase 3 study.

Although frequently prescribed to relieve acute pain in patients, non-steroidal anti-inflammatory drugs (NSAIDs) are associated with dose-related gastrointestinal, cardiovascular, and renal complications. Investigational, submicron particle NSAIDs are being developed that could provide effective pain relief at lower doses than currently available oral NSAIDs. This is the first phase 3 study evaluating the analgesic efficacy and safety of lower-dose indomethacin submicron particle capsules in patients following elective surgery. This multicenter, double-blind study enrolled patients aged 18 to 68 years who underwent bunionectomy under regional anesthesia. Patients with a pain intensity rating of ≥40 mm on a 100-mm Visual Analog Scale were randomized to receive indomethacin submicron particle capsules (40 mg 3 times daily [TID], 40 mg twice daily [BID], or 20 mg TID), celecoxib (400 mg loading dose, then 200 mg BID), or placebo. The primary efficacy parameter was the overall (summed) pain intensity difference measured by a Visual Analog Scale during a period of 48 hours. Scheduled assessments measured secondary efficacy parameters such as patient pain intensity differences. Indomethacin submicron particle capsules 40 mg 3 times daily (509.6 ± 91.9 overall [summed] pain intensity difference), 40 mg twice daily (328.0 ± 92.9 overall [summed] pain intensity difference), and 20 mg 3 times daily (380.5 ± 92.9 overall [summed] pain intensity difference) reduced pain intensity from 0 to 48 hours (P ≤ 0.046 for all 3 groups) compared with placebo (67.8 ± 91.4 overall [summed] pain intensity difference). There was some evidence of patient analgesia for celecoxib (279.4 ± 91.9 overall [summed] pain intensity difference; P = 0.103). Some evidence of pain control was observed in patients as early as 2 hours following administration of indomethacin submicron particle capsules and was sustained throughout the treatment period. Indomethacin submicron particle capsules were generally well tolerated by patients. These results suggest that lower-dose indomethacin submicron particle capsules are a potentially promising treatment option for patients with acute pain.