gms | German Medical Science

Problem: Diractin^® is a new, Transfersome^® based ketoprofen (KT) formulation for local application. Transfersome^® are carriers able to cross the skin driven by the transcutaneous moisture gradient avoiding drug clearance by the cutaneous microcirculation, and allowing targeted delivery into tissues like muscle and joints. The product was investigated in studies of knee osteoarthritis (OA) and other painful joint and musculoskeletal diseases with treatment duration of up to 36 months.

Methods:

Study 1: 6-week, placebo-controlled study in comparison to celecoxib This multi-center, randomized, double-blind, double-dummy, parallel group clinical study investigated patients with knee OA who were treated twice daily with placebo (n=127), celecoxib (100 mg; n=132), or Diractin^® (~100 mg KT/knee; n=138). Diractin^® showed statistically significantly greater improvement for both WOMAC pain and patient global assessment vs. placebo. The effect size was comparable to celecoxib.

Study 2: 12-week, placebo controlled study of 3 different dosages of Diractin^®. This multi-center, randomized, double-blind, parallel group study in patients with knee OA investigated twice daily dosages of 25 (n=223), 50 (n=223), and 100 mg KT/knee (n=221) compared to placebo (n=199). Both the 50 mg and 100 mg treatment groups showed statistically significantly greater improvement for WOMAC pain vs. placebo.

Study 3: >52-week comparative study to 1000 mg naproxen. This multi-center, randomized, double-blind, parallel group study in patients with knee OA randomized 349 patients. The study showed non-inferiority of Diractin^® (100 mg KT/knee twice daily) to 500 mg naproxen twice daily for WOMAC pain, WOMAC function and patient global assessment of response to therapy. Changes from baseline for WOMAC function showed even a trend for superiority of Diractin^® vs. naproxen (p=0.0536).

Study 4: 36 months open label study. This study enrolled 487 patients with joint and/or musculoskeletal pain or soft tissue inflammation (342 with knee OA). Pain reduction >30% was reported in 77.7%, a reduction of >50% in 59.1%, and a reduction >80% in 28% of the patients. This pain reduction improved the patients┤ quality of life in all categories, the strongest improvement observed for pain/discomfort (2.6% at screening, 20% at final visit). Treatment related adverse events (AEs) were mainly mild to moderate dermal reactions, mostly erythema, in 14.8% of the patients. None of the serious AEs was considered drug related. The KT plasma trough concentrations were very low (~30ng/ml). No phototoxic reactions were reported.

Results and conclusions: Diractin^® was safe and well tolerated for treatment periods of up to 36 months with efficacy comparable to 200 mg celecoxib or 1000 mg naproxen daily. There was no evidence of AEs related to systemic ketoprofen exposure. Most treatment related events were dermal irritations. Diractin^® appears to be a valuable option for the short and long-term treatment of knee OA and other local pain syndromes.