Efficacy and safety of diclofenac sodium 2% topical solution for osteoarthritis of the knee: a randomized, double-blind, vehicle-controlled, 4 week study.

OBJECTIVE: Nonsteroidal anti-inflammatory drugs (NSAIDs) are standard therapy for osteoarthritis (OA). Topically applied NSAIDs reduce systemic exposure compared with oral NSAIDS, and European guidelines recommend their use. The NSAID diclofenac is available in a range of topical formulations. Diclofenac 1% gel and 1.5% four times daily and 2% twice daily (BID) solutions are approved to reduce pain from OA of the knee(s). The objective of this study was to investigate the efficacy and safety of diclofenac sodium 2% topical solution BID versus vehicle control solution for treating pain associated with OA of the knee. RESEARCH DESIGN AND METHODS: A phase II, 4 week, randomized, double-blind, parallel-group, two-arm, vehicle-controlled study compared pain relief with diclofenac sodium 2% topical solution versus control (vehicle only) in patients aged 40 to 85 years with radiographically confirmed primary OA of the knee. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01119898. MAIN OUTCOME MEASURES: The primary efficacy outcome was change from baseline to the final visit in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale. Secondary outcomes included additional WOMAC subscales and patient global assessment of OA. Treatment-emergent adverse events (TEAEs), skin irritation, and vital signs were assessed and collected throughout the study. RESULTS: Of 260 patients randomized, 259 received ≥1 dose of study drug. Significantly greater reductions in least-squares mean (standard error) WOMAC pain scores were observed for diclofenac-treated (-4.4 [0.4]) versus vehicle-treated patients (-3.4 [0.4]) at the final visit (p = 0.040). The most commonly reported TEAEs were administration site conditions. The vehicle-treated group experienced slightly more TEAEs than the active treatment group (38.8% vs. 31.5%). No serious adverse events were reported. CONCLUSIONS: Administration of diclofenac sodium 2% topical solution BID resulted in significantly greater improvement in pain reduction in patients with OA of the knee versus vehicle control and was generally well tolerated.