LAS VEGAS, NV— Nano-sized drug particle nonsteroidal anti-inflammatory drugs (NSAIDs) could be effective in the management of pain and warrant further evaluation in Phase 3 trials, according a presentation at PAINWeek 2012.
Garen Manvelian, MD, from Iroko Pharmaceuticals, Philadelphia, and colleagues reported that NSAIDS are well established in the management of acute pain, but are also associated with dose-dependent risks for the development of cardiovascular, gastrointestinal and renal adverse events. The FDA has issued a Public Health Advisory stating that NSAIDs should be administered at the lowest effective dose for the shortest duration consistent with individual patient treatment goals.
Lower-dose, submicron particle NSAIDs are being developed using proprietary SoluMatrix technology, designed to offer effective pain relief at lower doses. The drug reformulation produces a super-fine powder of submicron-sized drug particles. Both diclofenac and naproxen have been developed with submicron particles.
Two Phase 2 trials were conducted to evaluate the efficacy and safety of investigational, submicron-particle oral diclofenac and naproxen in a validated post-surgical pain model. Data showed that submicron particle oral diclofenac and naproxen demonstrated good efficacy for the primary endpoint of sum of total pain relief (TOTPAR) at 12 hours, compared with placebo.
More than 450 patients (>200 in each trial) underwent extraction of >2 impacted third molars while under local anesthesia. Within 6 hours after extraction, patients with moderate-to-severe intensity pain (a score >50mm on a 100mm visual analog scale) were randomized to treatment. Patients received a single dose of submicron particle diclofenac (18 mg or 35 mg) or naproxen (200 mg or 400 mg), an active comparator (celecoxib 400 mg or standard naproxen 250 mg or 500 mg), or placebo. Patients assessed their pain relief relative to the study entry using a 5-point categorical scale (0=none and 4=complete relief of pain).
Safety and tolerability were generally comparable among the submicron particle NSAID treatment groups, comparators (celecoxib or standard naproxen), and placebo group. The degree of peak pain relief was higher for patients treated with the investigational, lower-dose, submicron-particle oral diclofenac or naproxen compared with placebo in this post-surgical pain model. Based on these results, Dr. Manvelian and colleagues added that further study is merited.