Background Non-steroidal anti-inflammatory drugs (NSAIDs) are frequently prescribed for the management of osteoarthritis (OA) pain. As a class, NSAIDs are associated with dose-related, serious gastrointestinal, cardiovascular, and renal adverse events (AEs), which has prompted the European Medicines Agency, the US Food and Drug Administration, and other organizations to recommend that NSAIDs be used at the lowest effective dose for the shortest possible duration . To deliver effective pain relief with lower systemic exposure than commercially available drug products, Iroko Pharmaceuticals is developing investigational, lower-dose SoluMatrix® meloxicam manufactured using SoluMatrix Fine Particle Technology™ and containing submicron particles of meloxicam with enhanced dissolution properties.
Objectives To evaluate the efficacy and safety of lower-dose submicron meloxicam in patients with OA pain.
Methods This randomized, double-blind, placebo-controlled, pivotal phase 3 study enrolled adults ≥40 years of age with radiographically confirmed (Kellgren-Lawrence grade II–III) hip or knee OA. Eligible patients were chronic NSAID and/or acetaminophen users with a baseline Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale score ≥40 mm (based on 100-mm Visual Analog Scale) and a documented OA pain flare (≥15-mm increase in WOMAC pain subscale score following washout of prior analgesics). Patients (N=403) were randomized 1:1:1 to receive once-daily treatment with lower-dose submicron meloxicam 5 mg (n=139), lower-dose submicron meloxicam 10 mg (n=130), or placebo (n=134). The primary efficacy endpoint was the mean change from baseline in WOMAC pain subscale score at week 12. Safety was also evaluated.
Results Overall, 350 patients (86.8%) completed the study. At week 12, lower-dose submicron meloxicam 5 mg (least squares [LS] mean [SE]: -36.36 [2.485]; P =0.0005) and 10 mg (-34.23 [2.677]; P =0.0059) provided significantly greater pain relief as measured by the primary endpoint compared with placebo (-25.49 [2.635]). In addition, pain was significantly improved based on the patient global impression of change with lower-dose submicron meloxicam 5 mg (P =0.0049) and 10 mg (P =0.0012) compared with placebo. Furthermore, patients in the lower-dose submicron meloxicam 5 mg (LS mean [SE]: 52.4 [6.61] doses; P =0.006) and 10 mg (48.4 [7.13] doses; P =0.0013) treatment groups used significantly less rescue medication compared with patients in the placebo group (73.2 [7.03] doses). Across all treatment groups, the most common AEs (occurring in ≥2% of patients) were diarrhea, headache, and urinary tract infection. No deaths or serious AEs were reported.
Conclusions Lower-dose submicron meloxicam 5 and 10 mg once daily provided significantly greater relief from OA pain compared with placebo and were generally well tolerated. These data suggest that lower-dose submicron meloxicam may represent a promising treatment option for adults with OA pain.
McCarberg BH, et al.Clin Ther. 2012;34(9):1954-1963.
Disclosure of Interest : R. Altman Consultant for: Ferring Pharmaceuticals; Iroko Pharmaceuticals, LLC; Johnson & Johnson; Novartis; Oletec; Petah Tikva; Pfizer; and Teva Pharmaceutical Industries Ltd, Speakers bureau: Ferring Pharmaceuticals, M. Hochberg Consultant for: AbbVie; Bioiberica SA; Eli Lilly; EMD Serono; Genentech/Roche; Iroko Pharmaceuticals, LLC; Merck & Co, Inc; Novartis Pharma AG; Pfizer; Pozen; and UCB, Inc, A. Gibofsky Shareholder of: AbbVie; Amgen; Bristol-Myers Squibb; GlaxoSmithKline plc; Johnson & Johnson; and Pfizer, Consultant for: AbbVie; Amgen; Genentech; Iroko Pharmaceuticals, LLC; Horizon; Takeda; and UCB, D. Parenti Employee of: Iroko Pharmaceuticals, LLC, C. Young Employee of: Iroko Pharmaceuticals, LLC