Acute pain relief by a proprietary, nano-formulated lower-dose oral diclofenac

Abstract

New NSAID formulations are being developed to improve tolerability while maintaining efficacy. The purpose of this clinical study was to evaluate time to onset of analgesia in an investigational, proprietary, nano-formulated, lower-dose, oral diclofenac compared with placebo in an acute pain model. This was a Phase 2, multicenter, randomized, double-blind, single-dose, parallel-group, active- and placebo-controlled study. Subjects (N=202) were 18-50 years old, had extraction of ≥2 third molars (≥1 of which was a fully or partially impacted mandibular third molar), and experienced moderate to severe pain intensity ≤6 hours post-surgery. Subjects assessed baseline pain intensity before receiving a single dose of nano-formulated lower dose diclofenac 18mg or 35mg, celecoxib 400mg, or placebo, and pain intensity and pain relief from 15 minutes through 12 hours. There was a statistically significant (P<0.001) shorter time to onset of analgesia (mean±SE) for nano-formulated lower dose diclofenac 35mg (42min±3.6), nano-formulated lower dose diclofenac 18mg (36min±3.0), and celecoxib 400mg (54min±4.2) compared with placebo (144min±9.0). There was also a statistically significant improvement in mean time to first perceptible pain relief, mean time to meaningful pain relief, and mean time to peak pain relief for nano-formulated diclofenac 18mg and 35mg when compared with placebo. Tolerability data were comparable for both nano-formulated diclofenac doses and celecoxib compared with placebo. Nano-formulated lower dose diclofenac demonstrated a faster time to onset of analgesia compared with placebo and was numerically better than celecoxib. Results from this Phase 2 clinical trial suggest that use of this nano-formulated, lower dose formulation may provide clinical benefit in the relief of mild to moderate acute pain. These results are in line with the FDA directive to use the lowest effective NSAID dose. Research funded by Iroko Pharmaceuticals.