Background Non-steroidal anti-inflammatory drugs (NSAIDs) are recommended for the management of pain associated with rheumatoid arthritis and osteoarthritis. As a class, NSAIDs are associated with dose-related serious gastrointestinal, cardiovascular, and renal adverse events (AEs), prompting the European Medicines Agency, the US Food and Drug Administration, and others to recommend that NSAIDs be used at the lowest effective dose for the shortest possible duration.1 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 pharmacokinetic (PK) properties and safety of lower-dose submicron meloxicam in healthy adult volunteers.
Methods In this 4-period, 4-sequence crossover study, healthy adults aged 18 to 55 years were randomized to receive single doses of lower-dose submicron meloxicam 5 mg (under fasted conditions), lower-dose submicron meloxicam 10 mg (under fasted and fed conditions), and conventional meloxicam 15-mg tablets (Mobic®); Boehringer Ingelheim; under fasted conditions). Blood samples for PK assessment were collected pre dose through 96 h post dose and were analyzed using a validated LC-MS/MS method. Safety was also evaluated.
Results Twenty-eight participants were enrolled and 25 participants completed the study. Lower-dose submicron meloxicam 10 mg (1.25±0.25 μg/mL) attained similar mean peak plasma meloxicam levels ± SD compared with conventional meloxicam 15-mg tablets (1.29±0.42 μg/mL; Table) under fasting conditions. Lower-dose submicron meloxicam 5 mg (2.0 h) and 10 mg (2.0 h) achieved more rapid time to peak plasma meloxicam levels under fasting conditions compared with conventional meloxicam 15-mg tablets (4.0 h). Lower-dose submicron meloxicam 10 mg demonstrated approximately 29% lower overall systemic exposure compared with conventional meloxicam 15-mg tablets (Table). As described for other NSAIDs, food decreased the rate but not the overall extent of meloxicam absorption from lower-dose submicron meloxicam (Table). Lower-dose submicron meloxicam 5 and 10 mg and conventional meloxicam 15-mg tablets demonstrated similar drug clearance based on half-life and the terminal elimination rate constant (Table). Treatment-related AEs included 1 case each of mild abdominal pain and mild diarrhea in the lower-dose submicron meloxicam 10 mg (fed) group and 1 report of mild somnolence in the lower-dose submicron meloxicam 5 mg group.
Conclusions Lower-dose submicron meloxicam 10 mg demonstrated comparable peak plasma levels, earlier time to peak plasma levels, and lower overall systemic exposure compared with conventional meloxicam 15-mg tablets under fasting conditions. Trials are underway to assess the clinical impact of this investigational, lower-dose meloxicam drug product.
McCarberg BH, et al. Clin Ther. 2012;34(9):1954-1963.
Disclosure of Interest K. Olugemo Employee of: PAREXEL, D. Parenti Employee of: Iroko Pharmaceuticals, LLC, C. Young Employee of: Iroko Pharmaceuticals, LLC