Background 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.1 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.
Objectives Evaluate safety of lower-dose submicron indomethacin in postsurgical patients.
Methods 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.
Results 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.
Conclusions 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.
Langford RM. Clin Rheumatol. 2006;25 Suppl 1:S2-8.
Acknowledgements The authors would like to thank Jennifer Nezzer, MS, and Daniel Solorio, whose contributions and individual efforts helped make these studies possible.
Disclosure of Interest : 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 & 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