Background/Purpose: Diclofenac sodium topical gel (DSG) 1% is clinically proven to be effective and well-tolerated for treatment of osteoarthritis pain and could be appropriate to treat acute conditions, such as ankle sprains and soft tissue injuries. Current treatment options include oral non-steroidal anti-inflammatory drugs (NSAIDs), which may be associated with an increased risk of systemic side effects (eg, gastrointestinal), and topically applied rubefacients, which could be ineffective. Previous pharmacokinetic studies have demonstrated that topically applied diclofenac gel results in low systemic exposure. Three randomized, placebo-controlled phase III clinical trials were conducted to assess the efficacy and safety of DSG 1% in subjects with acute ankle sprain or soft tissue injury/contusion. Safety data from the 3 controlled trials were pooled and are presented in this analysis.  

Methods: Two trials were conducted in ankle sprain and 1 trial in contusion. The 3 trials were similar in design and subject population except for the site of the acute injury.  Treatment was 3 g DSG 1% or placebo to affected ankle q.i.d. for 7 days or 2 g DSG 1% or placebo to the contusion q.i.d. for 2-7 days, until resolution. AEs were reported either during subject visits or in subject diaries in each trial.  The 3 AE databases were pooled for an overall safety analysis. Blood samples were collected for laboratory safety analyses before randomization and at end of study.

Results: Safety data were available for 615 subjects (mean age 30.9±12.0 years). A total of 7788 doses of DSG 1% (N=310) and 7670 doses of placebo (N=305) were applied over the 3 trials. There were no meaningful differences in the incidence of AEs between treatment groups. AEs occurred in 19 DSG 1% subjects (6.1%) and 16 placebo subjects (5.2%). Most were mild and self-resolving. Eight were considered treatment-related: 2 AEs in 1 DSG 1% subject (dry skin and erythema) and 6 AEs in 4 placebo subjects (application site pruritus, joint warmth, erythema, rash and pruritus [2]). There was 1 serious AE in the placebo group (distortion of wrist and rupture of scapholunate ligament), not considered to be treatment-related. Gastrointestinal, hepatic, and renal AEs were rare (≤2 events reported), while hematological and cardiac AEs were absent. Mean values for liver function test results, (alanine aminotransferase, aspartate aminotransferase, and total bilirubin) were within normal ranges at baseline and end of study and did not suggest any clinically significant systemic alterations during the course of the study. The overall safety profile of DSG 1% was similar to that of placebo.

Conclusion: DSG 1% applied 4 times daily for 7 days was found to be well-tolerated and no specific safety concerns were identified in these controlled clinical trials. Overall, the safety profile of DSG 1% demonstrates that it could be an appropriate treatment option for patients with acute painful conditions who have a need to minimize the systemic absorption of NSAIDS.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/pooled-safety-data-from-randomized-controlled-trials-of-diclofenac-sodium-topical-gel-1-in-subjects-with-acute-pain/