Presented at the 2013 AAPM Annual Meeting « Back

Diclofenac Submicron Particle Capsules Demonstrate Early and Sustained Acute Pain Relief

Charles Argoff, MD, pargoff@optonline.net¹, Stephen Silberstein, MD², Allan Gibofsky, MD³, Stephen Daniels,DO⁴, Steve Jensen⁵, Clarence L. Young, MD⁵, (1) Albany Medical College, Albany, New York, (2) Thomas Jefferson University, Philadelphia, Pennsylvania, (3) Hospital for Special Surgery, New York, New York, (4) Premier Research Group, Austin, Texas, (5) Iroko Pharmaceuticals, Philadelphia, Pennsylvania

Introduction: Early management of acute pain may impact the severity and duration of pain. NSAIDs are utilized to treat acute pain but have the potential for serious dose-related gastrointestinal, cardiovascular, and renal adverse events (AEs). Investigational submicron particle NSAIDs using proprietary SoluMatrix™ technology could provide effective pain relief at lower doses than currently available oral NSAIDs. We evaluated the analgesic efficacy of diclofenac submicron particle capsules in a model of moderate to severe post-surgical pain. Methods: This multi-center, double-blind, multiple-dose, study randomized 428 adult patients following bunionectomy surgery under regional anesthesia. Patients experiencing pain intensity of ≥40mm on a visual analog scale (VAS) received diclofenac submicron particle capsules (18 or 35mg TID), celecoxib (400mg loading dose; 200mg BID), or placebo. The primary endpoint was the summed pain intensity differences by VAS over 48h (VAS SPID-48). Results: All active treatment groups met the primary endpoint (VAS SPID-48; previously presented). Some pain relief (mean VAS PID) was apparent with diclofenac submicron particle 35mg (4.52) at 30min in contrast to celecoxib (0.80), diclofenac submicron particle 18mg (0.31), and placebo (0.12). At 4h after dose administration, diclofenac submicron particle 35mg provided better pain control (VAS PID) versus placebo (P=0.025). The most frequent treatment-emergent AEs were post-procedural edema, nausea, headache, and dizziness. Conclusions: Lower-dose, submicron particle diclofenac demonstrated better pain control over 48h with some evidence of analgesia as early as 30min after administration compared with placebo, and was generally well-tolerated. Diclofenac submicron particle capsules are a potentially promising therapeutic option for acute pain. References: 1) Hochberg MC. Prognosis of osteoarthritis. Annals of the rheumatic diseases. 1996;55(9):685-8. Epub 1996/09/01 2) Silverstein FE, Faich G, Goldstein JL, et al. Gastrointestinal Toxicity With Celecoxib vs Nonsteroidal Anti-inflammatory Drugs for Osteoarthritis and Rheumatoid Arthritis. JAMA: The Journal of the American Medical Association 2000;284:1247-55. 3) Schjerning Olsen A-M, Fosbøl EL, Lindhardsen J, et al. Duration of Treatment With Nonsteroidal Anti-Inflammatory Drugs and Impact on Risk of Death and Recurrent Myocardial Infarction in Patients With Prior Myocardial Infarction/Clinical Perspective. Circulation. 2011;123:2226–2235. PubMed 4) Schneider V, Levesque LE, Zhang B, Hutchinson T, Brophy JM. Association of selective and conventional nonsteroidal antiinflammatory drugs with acute renal failure: A population-based, nested case-control analysis. Am J Epidemiol. 2006;164(9):881-9. Epub 2.

Funding: Supported by Iroko Pharmaceuticals, LLC, Philadelphia, PA.