PALM SPRINGS, CA — Diclofenac, a commonly prescribed nonsteroidal anti-inflammatory drug (NSAID), was shown to provide acute pain relief when administered as a nanoformulated, lower-dose formulation, according to results of a study presented at the 2012 American Academy of Pain Medicine Annual Meeting.
Allan Gibofsky, MD, of the Hospital for Special Surgery in New York City, and colleagues performed a Phase 2 trial of nanoformulated lower-dose diclofenac vs. placebo. Nanoformulations use an investigational, proprietary technology to reduce particle size and enhance the dissolution of the drug within the body. New NSAIDs such as this nanoformulated lower-dose diclofenac are being developed to provide pain relief while improving tolerability.
This multicenter, randomized, double-blind, single-dose, parallel-group, active- and placebo-controlled study evaluated pain relief of the nanoformulated, lower-dose oral diclofenac (18mg or 35mg) compared with placebo and celecoxib in 202 adult patients in a validated acute-pain model. Diclofenac is currently available in 25mg and 50mg formulations.
Patients in this study 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. Patients were randomized to receive either nanoformulated lower-dose diclofenac 18mg or 35mg, celecoxib 400mg, or placebo. Prior to receiving therapy, patients assessed their baseline pain intensity. Pain intensity and pain relief were then recorded from 15 minutes through 12 hours.
In the intent-to-treat population, there was a significant difference in the mean visual analog scale (VAS) pain intensity difference (VASPID) score at 30 minutes for nanoformulated diclofenac 18mg compared with placebo (6.62±13.72 and -1.06±10.47, respectively; P=0.002). A significant difference for nanoformulated diclofenac 35mg and celecoxib 400mg was reached at 45 minutes (13.12±21.43 [P<0.001] and 5.49±16.39 [P=0.013], respectively). The statistically significant difference in mean VASPID for nanoformulated diclofenac 18mg and 35mg, as well as celecoxib 400 mg, was maintained for seven hours beginning at Time 0 (P<0.001). For all time points between 45 minutes through 7 hours, there was a significant difference in the mean VASPID for nanoformulated diclofenac 18mg or 35mg and celecoxib 400mg compared with placebo. Tolerability of both diclofenac and celecoxib was comparable to placebo.
Dr. Gibofsky et al reported that these results suggest that the use of nanoformulated, lower-dose diclofenac provides relief of acute pain and may offer a solution to improve tolerability of NSAIDs while maintaining efficacy.
“This diclofenac formulation may provide a clinical option consistent with the FDA directive to use the lowest effective NSAID dose,” the authors stated at their poster presentation. “These findings warrant further clinical development of nanoformulated lower-dose diclofenac in Phase 3 clinical trials for the management of mild to moderate acute and chronic pain.”