HONOLULU, HI — Using nano-formulated, lower-dose NSAIDs may provide clinical benefit for relieving mild to moderate acute pain, reported Garen Manvelian, MD, with Iroko Pharmaceuticals, Philadelphia, PA, at the American Pain Society’s 31st Annual Scientific Meeting.
Traditional non-steroidal anti-inflammatory drugs (NSAIDs), including naproxen, can have a variable onset of action and the potential for adverse events. Dr. Manvelian and colleagues conducted a Phase 2, multicenter, randomized, double-blind, single-dose, parallel-group, active- and placebo-controlled study to evaluate the time to onset of analgesia of an investigational, proprietary, nano-formulated, lower-dose, oral naproxen compared with placebo in an acute pain model. The primary efficacy endpoint was total pain relief over 0–12 hours (TOTPAR-12) based on patient-recorded VAS scores.
The study enrolled a total of 254 subjects aged 18–50 years old (mean age 21.1 years) that had extracted >2 third molars (>1 of which was a fully or partially impacted mandibular third molar), and had experienced moderate-to-severe pain intensity <6 hours post-surgery. The majority of patients were female (58.3%) and Caucasian (91.3%).
Baseline pain intensity was evaluated prior to receiving the first dose of nano-formulated lower dose naproxen 200mg or 400mg, traditional naproxen 250mg or 500mg, or placebo. Time to onset of analgesia, as well as pain intensity and pain relief from 15 minutes through 12 hours were evaluated. Adverse events were also assessed.
The nano-formulated lower-dose naproxen demonstrated superiority compared with placebo for TOTPAR-4, TOTPAR-8, and TOTPAR-12 (P<0.001). TOTPAR-12 scores for the nano-formulated 200mg and 400mg doses were 25.87+2 and 31.95+2, respectively, compared with 9.53+2 for placebo. Though both were superior to placebo, numerically higher mean VAS pain intensity difference scores were achieved with nano-formulated lower-dose naproxen 400mg (16.41+21.26) than standard naproxen 250mg (9.68+18.35) at 30 minutes. Results showed that there was a statistically significant faster mean time to first perceptible pain relief (mean+SE) for the nano-formulated lower-dose naproxen 400mg (30min+3; P<0.001) and 200mg (36min+3.6; P<0.05), and traditional naproxen 500mg (36min+3.6; P<0.001) compared with placebo (54min+6). The nano-formulated naproxen and traditional naproxen both also demonstrated faster mean time to first meaningful pain relief and time to peak pain relief compared with placebo.
Tolerability data were comparable for all treatment groups compared with placebo. Study results suggest that nano-formulated, lower dose NSAIDs may provide clinical benefit for relieving mild to moderate acute pain. Dr. Manvelian further noted that these study results were “in line with the FDA directive to use the lowest effective NSAID dose.”