A randomised trial comparing the efficacy and safety of topical ketoprofen in Transfersome(®) gel (IDEA-033) with oral ketoprofen and drug-free ultra-deformable Sequessome™ vesicles (TDT 064) for the treatment of muscle soreness following exercise.

We compared the effectiveness of topical ketoprofen in Transfersome(®) gel (IDEA-033) with oral ketoprofen and drug-free Sequessome™ vesicles (FLEXISEQ(®) Sport; TDT 064) in reducing calf muscle soreness. One hundred and sixty eight healthy individuals with a pain score ≥ 3 (10-point scale) 12-16 h post-exercise (walking down stairs with an altitude of 300-400 m) were randomised to receive IDEA-033 plus oral placebo (two dose groups), oral ketoprofen plus TDT 064, or TDT 064 plus oral placebo. The primary endpoint was muscle soreness reduction from pre-dosing to Day 7. Higher pain scores were recorded with oral ketoprofen plus TDT 064 (mean ± s 462.4 ± 160.4) versus IDEA-033 plus oral placebo (434.7 ± 190.8; P = 0.2931) or TDT 064 plus oral placebo (376.2 ± 159.1; P = 0.0240) in the 7 days post-exercise. Recovery from muscle soreness was longer with oral ketoprofen plus TDT 064 (mean 91.0 ± 19.5 h) versus IDEA-033 plus placebo (mean 81.4 ± 22.9 h; P = 0.5964) or TDT 064 plus placebo (mean 78.9 ± 22.8 h; P = 0.0262). In conclusion, ultradeformable phospholipid vesicles ± ketoprofen did not retard recovery from muscle soreness. TDT 064 improves osteoarthritis-related pain and could be of interest as a treatment for joint pain during and post-exercise.

Placebo controlled, crossover validation study of oral ibuprofen and topical hydrocortisone- 21-acetate for a model of ultraviolet B radiation (UVR)-induced pain and inflammation.

BACKGROUND: Pain related to ultraviolet B radiation (UVR) induced sunburn is an established, simple, acute pain model. One of the major criticisms is related to the potential dermal adverse events caused by the UVR exposure. This study tried to validate the model for oral and topical drugs and to define the minimum required UVR exposure. METHODS: This subject- and observer-blinded, placebo-controlled, crossover study evaluated 600 mg oral ibuprofen (IB) and topical hydrocortisone-21-acetate (HC) twice daily (bid) in 24 healthy volunteers. Treatment started immediately after irradiation and again at 12 hours, 24 hours, and 36 hours post-UVR. Assessment of hyperalgesia to heat and signs of inflammation (erythema, skin temperature) for all areas was performed after UVR and again at 6, 12, 24, 36, and 48 hours. Subjects returned within 4-11 days to the study site for the second period of the study. As in the first period, subjects received HC at one side and topical placebo on the other side, but oral treatment was crossed-over. RESULTS: The primary analysis failed to show the expected superiority of the IB-group vs the placebo group in period 1 of the study. Evaluating period 2 alone clearly showed the expected treatment effects of IB for erythema and heat pain threshold. The results were less pronounced for skin temperature. In contrast to IB vs oral placebo, there were no differences in treatment response between HC and topical placebo. UVR at all dosages induced profound erythema and reduction of heat pain threshold without causing blisters or other unexpected discomfort to the subjects. The changes were almost linear between 1 and 2 minimal erythema doses (MED), whereas the change from 2 to 3 MED was less pronounced. CONCLUSION: Use of 2 MED in upcoming studies seems to be reasonable to limit subjects' UVB exposure. The following procedural changes are suggested: Intensified training sessions before randomization to treatmentIncrease in sample size if they are crossover studiesSimplification in design (either oral or topical treatment).

A multiple-dose, open-label, safety, compliance, and usage evaluation study of epicutaneously applied Diractin (ketoprofen in Transfersome) in joint/musculoskeletal pain or soft tissue inflammation.

The risk of oral NSAID including Cox-2 inhibitors to cause gastrointestinal, renal or cardiovascular adverse events related to systemic drug exposure could be reduced by local application. But only few long-term studies have been published to show safety and efficacy for long-term use of topical NSAID s. Diractin (formerly IDEA-033) is a viscous, aqueous formulation for epicutaneous application of ketoprofen based on ultra-deformable, self-regulating carrier (Transfersome). This multiple-dose, open label study with treatment periods up to 18 months included 402 patients with joint pain, musculoskeletal pain, stiffness or soft tissue inflammation (age of 61.4+/-11.5 years). Most of the patients suffered from osteoarthritis (OA) of the knee (68.9%). Diractin was applied epicutaneously up to twice daily with a maximum dose of 220 mg ketoprofen per a maximum of 2 application sites. The mean pain score at baseline was 5.4+/-.4 on a 10 point categorical scale. During the study the pain score progressively improved up to week 36 (3.5+/-1.9) without a substantial further change during the rest of observation period of up to 18 months. The reduction of pain scores between week 0 (baseline) and at all later visits was statistically significant (P<0.0001). Patients also reported an improvement of quality of life on the EUROQoL. The majority of treatment related adverse events were skin and subcutaneous tissue disorders with the highest frequency reported for erythema (16.7%) and pruritus (2.0%). Systemic ketoprofen exposure remained low throughout the study period with plasma concentrations of less than 1% of what was reported for a single, standard oral dose of 200 mg ketoprofen. There were no occurrences of treatment related serious adverse events and no remarkable changes in laboratory values or vital signs. In summary, Diractin provided adequate pain relief with a good safety and tolerability profile when used for up to 18 months (72 weeks).

Efficacy of epicutaneous Diractin (ketoprofen in Transfersome gel) for the treatment of pain related to eccentric muscle contractions.

OBJECTIVE: To investigate the effect of epicutaneously applied Diractin (ketoprofen in Transfersome gel) on pain induced by eccentric muscle contractions. METHODS: Three pilot studies which were subsequently pooled for a meta-analysis compared the efficacy of a single application of 25 mg ketoprofen in Diractin to 25 mg oral ketoprofen and placebo for the treatment of pain induced by 50 eccentric contractions of the elbow flexor muscles. In addition, the effect of multiple usage of up to 100 mg ketoprofen in Diractin bid over seven days on pain induced by walking down stairs with a total altitude of 200 meters was investigated. RESULTS: A single dose of 25 mg ketoprofen in Diractin after the elbow flexion exercise was significantly superior to placebo from 5 to 12 hours after treatment and also to oral ketoprofen at some time points after treatment. In contrast, oral ketoprofen was not different to placebo at any time after treatment. Multiple doses of up to 100 mg ketoprofen Diractin provided significant more pain relief than placebo on muscle pain induced by walking down stairs. CONCLUSIONS: Eccentric exercise-induced muscle soreness was shown to be an appropriate acute pain model to evaluate the efficacy of nonsteroidal anti-inflammatory drugs applied epicutaneously with Transfersome carriers. Diractin proved to be efficacious in relieving pain from eccentric muscle contractions and muscle over-exercise, respectively. The effect needs to be confirmed in a larger prospective clinical trial.