title: A phase 2 study of lower-dose, indomethacin submicron particle capsules demonstrates early onset of acute pain relief.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: *MIG Clinical Research Consulting, San Diego †Division of Rheumatology & Clinical Immunology, University of Maryland School of Medicine, Baltimore, MD ‡Premier Research Group International, LLC, Austin, TX §UCLA Medical Center RHU, Los Angeles, CA ∥Iroko Pharmaceuticals LLC, Philadelphia, PA.
authors.forename: Garen
authors.initials: G
authors.lastname: Manvelian
authors.forename: Marc C
authors.initials: MC
authors.lastname: Hochberg
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Daniels
authors.forename: Roy D
authors.initials: RD
authors.lastname: Altman
authors.forename: Clarence L
authors.initials: CL
authors.lastname: Young
mesh_terms: D000293:Adolescent; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D002214:Capsules / Q000008:administration & dosage; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007213:Indomethacin / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010147:Pain Measurement; D010149:Postoperative Pain / Q000188:drug therapy*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D002214:Capsules; D007213:Indomethacin