Background IDEA 033 is a formulation of ketoprofen in Transfersome – ultra-deformable carriers – that is applied epicutaneously for the treatment of pain associated with OA, thus minimising the potential for systemic adverse events (AEs) associated with non-steroidal anti-inflammatory drugs (NSAIDs).
Objectives To compare 3 doses of IDEA 033 (25mg, 50mg and 100mg ketoprofen in Transfersome gel) with orally administered naproxen and placebo for treating the signs and symptoms of OA of the knee.
Methods A multicentre, randomised, double-blind, double-dummy, parallel-group, placebo- and active-controlled study in patients having radiographic evidence of OA in both knees for ≥6 mo and meeting ACR Functional Class I–III OA criteria. Patients had at least moderate pain (2) on a 5-point Likert scale when not taking NSAIDs at screening and met OA flare criteria at baseline [WOMAC pain subscale ≥40 mm (based on a normalised 0–100 mm VAS scale) and ≥15 mm greater than at screening]. Patients received 12 wks of therapy twice daily with 25mg, 50mg or 100mg ketoprofen in Transfersome plus oral placebo; epicutaneous placebo (Transfersome gel without ketoprofen; TDT 064) plus oral placebo (combined placebo); or oral 500mg naproxen plus TDT 064. WOMAC pain was assessed at baseline and wks 2, 4, 8 and 12. Patients’ response to therapy was measured on a 5-point Likert scale at wks 2, 6, 9 and 12.
Results There were 837 patients in the intent-to-treat (ITT) and safety populations. Baseline median WOMAC pain subscale scores were high (Table). At 2 wks, all groups showed substantial decreases in pain with small changes in pain scores thereafter. The a priori hypothesis test (ITT population) showed no statistically significant improvement between ketoprofen in Transfersome and combined placebo. The naproxen plus TDT 064 arm was significantly superior to the ketoprofen in Transfersome arms and combined placebo arm. The combined placebo arm had the lowest rate of AEs (Table). Serious AEs were considered not/unlikely to be related to study treatment.
Conclusions Epicutaneously applied ketoprofen (25mg, 50mg and 100mg) in Transfersome (IDEA 033) for 12 wks was not statistically superior to combined treatment with epicutaneous placebo (TDT 064) and oral placebo, possibly owing to the substantial change from baseline reported for the combination of TDT 064 and oral placebo, high baseline pain severity and high protocol violation/dropout rate (ITT population). All treatments were well tolerated. Investigation of the apparent beneficial effect of epicutaneous placebo (TDT 064) is ongoing.
Disclosure of Interest M. Rother Shareholder of: IDEA AG (sponsor of the trial), Employee of: IDEA AG (sponsor of the trial) at the time of trial conduct, G. Yeoman: None Declared, E. Ekman Grant/Research support from: Funding for conduct of the clinical study was provided by IDEA