Evaluation of the safety and efficacy of an intravenous nanocrystal formulation of meloxicam in the management of moderate-to-severe pain after bunionectomy

Journal of Pain Research Evaluation of the safety and efficacy of an intravenous nanocrystal formulation of meloxicam in the management of moderate-to-severe pain after bunionectomy Ira J Gottlieb 2 Deborah R Tunick 2 Randall J Mack 1 Stewart W McCallum 1 Campbell P Howard 0 Alex Freyer 1 Wei Du 3 0 Howard Medical Consulting for the Pharmaceutical Industry , Yardley, PA , USA 1 Recro Pharma, Inc. , Malvern, PA , USA 2 Chesapeake Research Group , Pasadena, MD , USA 3 Clinical Statistics Consulting , Blue Bell, PA , USA 8 1 0 2 - l u J - 2 1 n o 7 0 2 . 6 4 . 9 5 . 7 3 y b / m o c . s s rvepe l.yno PowerdbyTCPDF(ww.tcpdf.org) Objective: This randomized, double-blind, placebo-controlled study evaluated the safety and efficacy of an intravenous (IV) nanocrystal formulation of meloxicam in subjects with moderateto-severe pain following a standardized unilateral bunionectomy. Methods: Fifty-nine subjects aged 18-72 years were randomized to receive doses of either 30 mg (n=20) or 60 mg (n=20) meloxicam IV or placebo (n=19), administered once daily as bolus IV injections over 15-30 seconds (two or three doses). Safety, the primary objective, was assessed by physical examination, clinical laboratory tests, and the incidence of adverse events (AEs). Efficacy was evaluated by examining summed pain intensity differences over the first 48 hours (SPID48) using analysis of covariance models. Use of opioid rescue analgesic agents was evaluated. Results: Generally, AEs were mild-to-moderate in intensity, and their incidence was similar across the three treatment groups. No serious AEs were reported; there were no withdrawals due to AEs, including injection-related AEs. The estimated effect size for SPID48 versus placebo was 1.15 and 1.01 for meloxicam IV doses 30 mg and 60 mg, respectively (P≤0.01). Both doses produced significantly greater pain reductions versus placebo (P≤0.05) at all evaluated times/ intervals during the 48-hour period. The proportions of subjects with ≥30% and ≥50% overall reduction in pain from baseline after 6 and 24 hours were significantly higher with meloxicam IV 30 mg doses versus placebo, but not with meloxicam IV 60 mg doses. The time to first use of rescue medication was significantly longer versus placebo with meloxicam IV 60 mg (P<0.05), but not with meloxicam IV 30 mg doses. Conclusion: Meloxicam IV was generally safe and well tolerated in subjects with moderateto-severe post-bunionectomy pain. Once-daily administration of meloxicam IV 30 mg and 60 mg exhibited rapid onset of analgesia (as early as 15 minutes) with maintenance of analgesic effect for two consecutive 24-hour periods. - Video abstract Point your SmartPhone at the code above. If you have a QR code reader the video abstract will appear. Or use: http://youtu.be/Jzis0VDClXI the mainstay of peri- and postoperative pain management, opioid-related adverse events (AEs) such as respiratory depression, sedation, nausea/vomiting, and constipation can potentially limit the benefit of these medications. Thus, there is a need for non-opioid analgesics that provide pain control while reducing the risk of AEs.5,6 Selection of pain control strategies for bunion surgery – which include local infiltration of anesthetics and/or periph810 eral nerve block procedures,1,7,8 opioids,9–11 nonsteroidal l-Ju2 anti-inflammatory drugs (NSAIDs),12 and various other -12 analgesics (eg, acetaminophen) – is generally guided by the no7 intensity of the post-bunionectomy pain, the duration of the .026 analgesia provided, and the tolerability and patient acceptance .459 of the chosen strategy. Patient acceptance of opioid analgesics .37 may be influenced by AEs such as respiratory depression, /yb nausea/vomiting, urinary retention, dysphoria, and possible .com long-term dependence. Potential AEs of nonselective (ie, ss COX-1 and COX-2 inhibitors) NSAIDs include impaired rvepe l.yno platelet and renal function, and gastrointestinal intolerance, ./dowww lsueano tolerability of the chosen medication is crucial for attaining which could limit patient acceptance of these agents. Patient / ttsp rspe rapid and adequate pain relief. : ohm roF Meloxicam, a preferential COX-2 inhibitor with analgesic, frd antipyretic, and anti-inflammatory properties, with better gasaed trointestinal tolerability compared with nonselective NSAIDs, lonw has been proven effective when administered orally for amedo liorating the signs and symptoms of rheumatoid arthritis and rcha osteoarthritis.13–16 However, largely due to its poor solubility, see orally administered meloxicam is not rapidly absorbed; peak ianR plasma concentrations after a dose of 30 mg are not reached foP until 9–11 hours after administration.14,17,18 Consequently, this lran slow onset of action is a reason why oral meloxicam is not Juo currently approved for the management of acute pain. A novel nanocrystal colloidal dispersion formulation of meloxicam (N1539; Recro Pharma, Inc., Malvern, PA, USA) has recently be (...truncated)