A 12-week randomized study of topical therapy with three dosages of ketoprofen in Transfersome® gel (IDEA-033) compared with the ketoprofen-free vehicle (TDT 064), in patients with osteoarthritis of the knee

Werner Kneer, Matthias Rother, Stefan Mazgareanu, Egbert J Seidel, European IDEA-033 study group, Werner Kneer, Matthias Rother, Stefan Mazgareanu, Egbert J Seidel, European IDEA-033 study group

Abstract

Objective: To evaluate the safety and efficacy of ketoprofen in Transfersome® gel (IDEA-033) in comparison with a ketoprofen-free vehicle (TDT 064) for the treatment of osteoarthritis (OA) of the knee.

Methods: Patients with knee OA (N = 866) were randomly assigned to receive topical IDEA-033 containing 100, 50, or 25 mg ketoprofen, or TDT 064 twice daily for 12 weeks, in a double-blind trial. The primary efficacy endpoint was the change in the Western Ontario and McMaster Universities (WOMAC®) Osteoarthritis Index pain subscale score. The coprimary efficacy endpoints were the WOMAC function subscale score and the patient global assessment of response to therapy. The secondary endpoints included the numeric pain rating for the first 14 days of treatment and the Outcome Measures in Rheumatology (OMERACT)-Osteoarthritis Research Society International (OARSI) responder rates.

Results: The WOMAC pain scores were reduced by approximately 50% or more in all four groups. The 100 and 50 mg ketoprofen groups, but not the 25 mg group, showed a superior reduction in the WOMAC pain score versus the TDT 064 group (100 mg: -57.4% [P = 0.0383]; 50 mg: -57.1% [P = 0.0204]; and 25 mg: -53.4% [P = 0.3616] versus TDT 064: -49.5%). The superiority of the ketoprofen-containing formulations was not demonstrated for the WOMAC function subscale score, whereas the patient global assessment of 50 mg ketoprofen group, but not the 100 or 25 mg group, was superior to that of the TDT 064 group (P = 0.0283). Responder rates were significantly higher for all the IDEA-033 groups versus the TDT 064 group, but were high in all groups (100 mg: 88.6%; 50 mg: 86.8%; 25 mg: 88.6%; and TDT 064: 77.5%). Dermal reactions were the only relevant drug-related adverse events in all four groups.

Conclusion: The 50 and 100 mg ketoprofen doses of IDEA-033 were only marginally superior to TDT 064 for reducing pain associated with knee OA. The study indicates a high treatment response to the topical ketoprofen-free vehicle TDT 064.

Keywords: Sequessome™; drug-free; medical device; non-steroidal anti-inflammatory drugs; pain.

Figures

Figure 1
Figure 1
Flow of patients enrolled in the study. Notes:aOne patient withdrew consent prior to treatment. IDEA-033 (IDEA AG, Munich, Germany); TDT 064 (Pro Bono Bio Entrepreneur Ltd, London, UK). Abbreviation: AEs, adverse events.
Figure 2
Figure 2
Responder rate,a according to the modified OMERACT-OARSI-criteria (ITT population). Notes:aAnalyzed by visit, using a multiple regression model, with treatment group and baseline OA pain as the explanatory variables; bstatistically significant difference compared with the TDT 064 vehicle. IDEA-033 (IDEA AG, Munich, Germany); TDT 064 (Pro Bono Bio Entrepreneur Ltd, London, UK). Abbreviations: ITT, intent-to-treat; OA, osteoarthritis; OMERACT, Outcome Measures in Rheumatology; OARSI, Osteoarthritis Research Society International.

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