THU0337 Lower-Dose Solumatrix® Indomethacin: Combined Safety Data from Two Phase 3 Studies in Patients with Acute Pain following Elective Surgery: Table 1
Authors: R. Altman, A. Gibofsky, D. Parenti, C. Young
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Indomethacin, a potent non-steroidal anti-inflammatory drug (NSAID) used to treat acute pain, is, like other NSAIDs, associated with dose-dependent gastrointestinal (GI), cardiovascular (CV), and renal adverse events (AEs). US and EU health authorities recommend NSAIDs be used at the lowest effective dose.<sup>1</sup> To deliver effective pain relief with lower systemic exposure than commercially available drug products, Iroko Pharmaceuticals is developing investigational, lower-dose SoluMatrix® indomethacin using SoluMatrix Fine Particle Technology™, containing submicron particles of indomethacin with enhanced dissolution properties. We present safety and tolerability data from two phase 3 studies evaluating the efficacy of lower-dose submicron indomethacin in patients with acute pain following elective surgery. <h3>Objectives</h3> Evaluate safety of lower-dose submicron indomethacin in postsurgical patients. <h3>Methods</h3> Two phase 3, randomized, multicenter, double-blind studies enrolled patients 18–68 years old undergoing bunionectomy. Patients with moderate-to-severe pain (≥40 mm/100-mm Visual Analog Scale) received lower-dose submicron indomethacin (40 mg TID, n=187, or BID, n=184, or 20 mg TID, n=183), placebo (n=188), or, in 1 study, celecoxib (400 mg loading dose followed by 200 mg BID, n=93). AEs, vital signs, pain intensity, and rescue medication use were monitored for 48 hours. Treatment-emergent AEs (TEAEs) were summarized by severity and seriousness. <h3>Results</h3> TEAEs were similar across treatment groups. The most common TEAEs (≥5% of patients in any treatment group) were nausea, post-procedural edema, headache, dizziness, vomiting, post-procedural hemorrhage, and constipation (Table). Seven (0.8%) patients withdrew due to a TEAE, including 2 cases of urticaria and 1 case each of uvulitis, angioedema, and nausea among recipients of lower-dose submicron indomethacin, and 1 case each of pyrexia and anxiety in the placebo group. A serious TEAE, a single report of deep vein thrombosis, in the lower-dose submicron indomethacin 40 mg BID group was determined to be unrelated to the study drug. <h3>Conclusions</h3> Lower-dose submicron indomethacin was generally well tolerated in two phase 3 studies in patients with postsurgical pain. There were no serious CV, GI, or renal AEs associated with NSAID use. Based on available efficacy data, the investigational lower-dose submicron indomethacin represents a potentially promising lower-dose option for treating acute pain. <h3>References</h3> Langford RM. Clin Rheumatol. 2006;25 Suppl 1:S2-8. <h3>Acknowledgements</h3> The authors would like to thank Jennifer Nezzer, MS, and Daniel Solorio, whose contributions and individual efforts helped make these studies possible. <h3>Disclosure of Interest</h3> : R. Altman Consultant for: Pfizer, Teva Pharmaceutical Industries Ltd, and Iroko Pharmaceuticals, LLC, A. Gibofsky Shareholder of: GlaxoSmithKline, Amgen, Bristol-Meyers Squibb, Pfizer, Abbvie, and Johnson &amp; Johnson, Consultant for: Takeda, Amgen, AbbVie, Genentech, Horizon, UCB, and Iroko Pharmaceuticals, LLC, D. Parenti Employee of: Iroko Pharmaceuticals, LLC, C. Young Employee of: Iroko Pharmaceuticals, LLC <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5355