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

Abstract

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.

Keywords: :

• Diclofenac sodium 2% topical solution
• Efficacy
• Knee osteoarthritis
• Safety

Transparency

Declaration of funding

This manuscript was supported by Horizon Pharma USA Inc. This study was supported by Mallinckrodt Pharmaceuticals.

Author contributions: L.T.W. was an investigator in the trial, contributed significantly to the data analysis plan, interpretation of results, and writing of the manuscript. J.D.K. contributed significantly to the data analysis plan and interpretation of results. R.J.H. contributed significantly to the data analysis plan, interpretation of results, and writing of the manuscript.

Declaration of financial/other relationships

L.T.W. has disclosed that he has no significant relationships with or financial interests in any commercial companies related to this study or article. J.D.K. has disclosed that he is a current employee of Horizon Pharma USA Inc. and holds stock in Horizon Pharmaceuticals. R.J.H. has disclosed that he has received consulting fees from Cadence Pharmaceuticals Inc., Horizon Pharma USA Inc., Hospira, Novartis, and Pozen Pharmaceuticals Inc., and is a previous employee of Searle/Pfizer. He has no financial interests in any of these companies.

CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgments

Mary Hines and Alan J. Klopp PhD of inScience Communications, Springer Healthcare provided medical writing support funded by Horizon Pharma USA Inc.

Previous presentation: Data from this study were published as an abstract and poster at the 33rd Annual Scientific Meeting of the American Pain Society (APS), 30 April–3 May 2014, Tampa, FL, USA (Poster #484).

Notes

*Pennsaid is a registered trademark of Horizon Pharma USA Inc., Deerfield, IL, USA

*Voltaren Gel is a registered trademark of Novartis Consumer Health Inc., Parsippany, NJ, USA