title: A phase 2 study of naproxen submicron particle capsules in patients with post-surgical dental pain.
abstract: BACKGROUND
  Naproxen is an NSAID with documented efficacy in pain management; however, it is associated with serious dose-related adverse events. A lower-dose naproxen drug product with comparable efficacy to commercially available naproxen could address these concerns. We studied the efficacy and safety of naproxen submicron particle capsules in patients with acute post-surgical dental pain.
  
  
  METHODS
  A phase 2, multicenter, randomized, single-dose study (NCT01229228) enrolled 254 patients (18-34 years old) undergoing third molar extraction. Patients who experienced moderate-to-severe pain ≤6 h following surgery received naproxen submicron particle capsules 200 or 400 mg, naproxen tablets 250 or 500 mg, or placebo. The primary efficacy parameter was patient-reported total pain relief over 0-12 h following administration of study medication. Secondary efficacy parameters included patient-reported total pain relief over 0-4 and 0-8 h; pain intensity assessments from 0 to 4, 0 to 8, and 0 to 12 h; and time to onset of analgesia. Safety and tolerability were also assessed.
  
  
  RESULTS
  Naproxen submicron particle capsules 200 mg (25.9 ± 2.0; 95% CI 21.9-29.8), naproxen tablets 250 mg (24.4 ± 2.0; 95% CI 20.4-28.3), naproxen submicron particle capsules 400 mg (31.9 ± 2.0; 95% CI 28.1-35.8), and naproxen tablets 500 mg (28.5 ± 2.0; 95% CI 24.7-32.4) groups experienced greater pain relief over 12 h compared with placebo (P < 0.001). Similar trends were observed for secondary outcomes of total pain relief over 0-4, 0-8 h, and time to onset of analgesia. Adverse events were generally similar across all treatment groups.
  
  
  CONCLUSIONS
  Lower-dose naproxen submicron particle capsules provided effective analgesia in acute post-surgical dental pain and warrant further evaluation as a potentially promising treatment for acute pain conditions.
authors.affiliation: Iroko Pharmaceuticals, LLC, One Kew Place, 150 Rouse Boulevard, Philadelphia, PA, 19112, USA, cyoung@iroko.com.
authors.forename: Clarence L
authors.initials: CL
authors.lastname: Young
authors.forename: Vibeke
authors.initials: V
authors.lastname: Strand
authors.forename: Roy
authors.initials: R
authors.lastname: Altman
authors.forename: Stephen
authors.initials: S
authors.lastname: Daniels
mesh_terms: D000293:Adolescent; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D002214:Capsules; D005260:Female; D006801:Humans; D008297:Male; D008964:Molar, Third / Q000601:surgery*; D009288:Naproxen / Q000008:administration & dosage*; D010147:Pain Measurement; D010149:Postoperative Pain / Q000188:drug therapy*; D013607:Tablets; D014081:Tooth Extraction; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D002214:Capsules; D013607:Tablets; D009288:Naproxen