Diclofenac in nano-formulated doses provides effective pain relief

A novel formulation of diclofenac provides pain relief at lower-than-standard doses during a Phase II clinical study as reported today at the 2011 World Congress on Osteoarthritis. The Congress is organized by the Osteoarthritis Research Society International.

The diclofenac study is part of a multi-drug development program at Iroko Pharmaceuticals to use proprietary nanotechnology in re-formulating a large class of pain medicines called NSAIDs (non-steroidal anti-inflammatory drugs). Nano-formulations reduce drug particle size to enhance drug dissolution in the body.

The Iroko program aims to use the proprietary SoluMatrix™ technology to lower the dosing of NSAIDs, reduce systemic exposure by 20%, and thus improve their safety and tolerability while maintaining their effectiveness. The US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) both have advised that NSAIDs should be administered at the lowest effective dose for the shortest duration of time^.

"Nano-formulations of NSAIDs may provide a new option for physicians as they balance efficacy and safety in treating pain," said Dr. Allan Gibofsky, Professor of Medicine and Public Health at Weill Medical College of Cornell University. "Iroko's results with nano-formulated diclofenac indicate this potential and merit larger-scale studies."

Diclofenac in standard formulations is an NSAID that has long been used in various pain-relief indications including osteoarthritis. Standard, currently marketed formulations of diclofenac are typically prescribed in 25 mg and 50 mg doses.

In the Phase II study reported at the Congress, diclofenac in nano-formulated doses of 18 mg and 35 mg was compared to placebo. The primary efficacy endpoint was total pain relief as reported at intervals over 12 hours (TOTPAR-12) by patients with acute dental pain following third-molar extraction. The improvement in pain relief associated with each of the two lower dose nano-formulations of diclofenac was highly statistically significant (p<0.001).

Also included in the study was the pain remedy celecoxib, at a dose of 400 mg. Although the study was not sized to show statistically significant differences between active drug treatments, both of the lower-dose nano-formulations of diclofenac showed numerically better scores than celecoxib by TOTPAR-12 assessment.

TOTPAR scores were also evaluated at eight hours and four hours. By those measurements as well, the nano-formulations of diclofenac showed statistically significant superiority to placebo and numerical superiority to celecoxib.

Another assessment used during the study was the time to onset of pain relief. This time was significantly shorter for all the active treatments than for placebo (p<0.001) and numerically shorter for both of the lower dose nano-formulations of diclofenac than for celecoxib.

Further data from Phase II clinical studies of nano-formulated NSAIDs under development by Iroko will be presented at another major medical conference this year.

Iroko has initiated several Phase III trials of nano-formulated NSAIDs manufactured using the proprietary SoluMatrix nano-technology platform of Iroko's partner, iCeutica. All these product candidates are designed for administration at lower doses without compromising onset of action and effectiveness, in keeping with the public-health advisories of the FDA and the EMA.