title: Efficacy and safety of low-dose submicron diclofenac for the treatment of osteoarthritis pain: a 12 week, phase 3 study.
abstract: OBJECTIVE
  NSAIDs, such as diclofenac, are the most commonly used medications to treat osteoarthritis (OA), but they are associated with dose-related adverse events (AEs). Low-dose submicron diclofenac was developed using a new, proprietary dry milling process that creates submicron drug particles (SoluMatrix Fine Particle Technology * ), enabling effective treatment at lower doses than other commercially available diclofenac drug products. This phase 3 study evaluated the efficacy and safety of low-dose submicron diclofenac 35 mg three times daily (tid) and twice daily (bid) in patients with OA pain.
  
  
  METHODS
  This double-blind study enrolled patients ≥40 years of age with clinically and radiographically confirmed (Kellgren-Lawrence grade II-III) hip or knee OA. Eligible patients were chronic NSAID and/or acetaminophen (APAP) users with baseline Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC) pain subscale scores ≥40 mm by visual analog scale and an OA flare (≥15 mm increase in WOMAC pain subscale score following discontinuation of NSAIDs/APAP at screening). Patients were randomized to submicron diclofenac 35 mg tid, submicron diclofenac 35 mg bid, or placebo for 12 weeks. ClinicalTrials.gov identifier: NCT01461369.
  
  
  METHODS
  Efficacy parameters included mean change from baseline in WOMAC pain subscale score at week 12 (primary efficacy parameter) and in average total WOMAC score over 12 weeks.
  
  
  RESULTS
  Submicron diclofenac 35 mg tid significantly improved WOMAC pain subscale scores from baseline at 12 weeks (-44.1; p = 0.0024) compared with placebo (-32.5). Submicron diclofenac 35 mg bid provided numerical improvement in pain at week 12 that did not reach statistical significance (-39.0; p = 0.0795) compared with placebo. Submicron diclofenac 35 mg tid (-35.9; p = 0.0002) and 35 mg bid (-30.3; p = 0.0363) improved the average total WOMAC score in treated patients over 12 weeks compared with placebo (-23.2). The most frequent AEs in the submicron diclofenac-treated groups were diarrhea, headache, nausea, and constipation. The inclusion of patients with a documented requirement for analgesic therapy (OA 'flare') at baseline and the high rates of rescue medication usage in the placebo group may have impacted the study outcome for the submicron diclofenac treatment groups.
  
  
  CONCLUSIONS
  Low-dose submicron diclofenac is an effective therapeutic option for the treatment of OA pain.
authors: Weill Medical College of Cornell University and Hospital for Special Surgery , New York, NY , USA.
authors: Allan
authors: A
authors: Gibofsky
authors: Marc C
authors: MC
authors: Hochberg
authors: Mark J
authors: MJ
authors: Jaros
authors: Clarence L
authors: CL
authors: Young
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000627:therapeutic use; D002626:Chemistry, Pharmaceutical; D004008:Diclofenac / Q000008:administration & dosage* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015207:Osteoarthritis, Hip / Q000188:drug therapy*; D020370:Osteoarthritis, Knee / Q000188:drug therapy*; D010147:Pain Measurement; D016896:Treatment Outcome
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004008:Diclofenac
keywords: Chronic pain; Diclofenac capsules; NSAID; Osteoarthritis; Submicron