A Phase 2 Study of Lower-dose, Indomethacin Submicron Particle Capsules Demonstrates Early Onset of Acute Pain Relief

摘要

Objectives: Nonsteroidal anti-inflammatory drugs are efficacious for the treatment of acute and chronic pain; however, they have the potential for serious adverse events (AEs). The objective of this study was to evaluate the efficacy and safety of investigational, lower-dose, indomethacin submicron particle capsules compared with placebo in a study of patients with postsurgical pain.Materials and Methods: This phase 2, multicenter, randomized, double-blind, single-dose, and placebo-controlled study enrolled 203 patients (18 to 50 y old) following extraction of >2 third molars who experienced moderate-to-severe pain intensity <6 hours after surgery. Patients received indomethacin submicron particle capsules (20 or 40 mg), celecoxib 400 mg, or placebo. The primary efficacy endpoint was the sum of total pain relief over 0 to 8 hours (TOTPAR-8) determined from the area under the curve for pain relief over 0 to 8 hours following administration of the study drug, where pain relief was measured on a 0 to 4 scale. Safety and tolerability were also assessed.Results: Mean ± SE TOTPAR-8 scores were 10.8 ± 1.4 (indomethacin submicron particle capsules 20 mg), 12.6 ±1.3 (indomethacin submicron particle capsules 40 mg), 14.8 ± 1.3 (celecoxib), and 3.0 ± 1.3 (placebo; P < 0.001 for active treatments vs. placebo). Indomethacin submicron particle capsules treatment groups demonstrated better mean TOTPAR over 4 hours than placebo(P < 0.001). Similar rates and profiles of treatment-emergent AEs were reported by patients across treatment groups.Discussion: Lower-dose, indomethacin submicron particle capsules provide good overall pain relief in patients with postsurgical pain and are generally well tolerated. Indomethacin submicron particle capsules are a potentially promising option for treatment of acute pain and warrant further study.