A Long-Term, Open-Label Study to Confirm the Safety of Topical Diclofenac Solution Containing Dimethyl Sulfoxide in the Treatment of the Osteoarthritic Knee

Abstract

To assess the long-term safety of a topical solution of diclofenac sodium in a vehicle containing dimethyl sulfoxide (TDiclo), subjects with radiologically confirmed, symptomatic osteoarthritis of the knee(s) applied the clinical dose of TDiclo (40 drops, four times daily) to each painful knee for up to 52 weeks. Safety assessment included adverse events, skin irritation scores of the treated knee(s), ocular examinations, and routine laboratory tests. There were 793 subjects (mean age, 62.5 years) who applied TDiclo to one or both (72%) knees for an average of 204 days, including 463 subjects for 6 months and 144 for 1 year. The most frequent adverse events were at the application site with no increase in incidence with prolonged exposure: dry skin (25.3%), contact dermatitis without vesicles (13.0%) or with vesicles (9.5%). Skin irritation score was 0 (normal) in 61.0% of subjects, 0.5 (dryness or flaking) in 23.9%, 1 or 2 (erythema without or with induration) in 6.9%, and 3 or 4 (erythema with induration and vesicles/bullae) in 8.2%. Subject dropouts included 114 (14.4%) with an application site skin adverse event. Individual subject laboratory test shift to abnormal occurred for hemoglobin (3.2%), aspartate aminotransferase (6.4%), alanine aminotransferase (7.3%), and creatinine (4.2%), but few shifts (less than 0.3% per variable) were clinically significant. No increased risk of cardiovascular or cataract events was noted. This long-term study of TDiclo revealed a safety profile comparable to that shown in multiple, shorter, well-controlled, double-blind trials with the predominant adverse effect noted being an application site reaction.