Research Article
Devineni D, Curtin CR, Ariya
Abstract
Background: A fixed-dose combination (FDC) tablet formulation of canagliflozin, a selective inhibitor of sodium glucose co-transporter 2 (SGLT2), and metformin can potentially provide complimentary mechanism of action to improve glycemic control in adults with type 2 diabetes mellitus. Objectives: To assess the bioequivalence of immediate release (IR) FDC tablets containing canagliflozin and metformin relative to co-administration of individual tablets of IR canagliflozin and metformin in healthy fed participants. Methods: The six studies were randomized, open-label, single-center, single-dose, 2-treatment, 2-period crossovertrials conducted in healthy male and female participants under fed conditions. Pharmacokinetics of canagliflozin and metformin were investigated following administration of 2 canagliflozin/metformin IR FDC tablets (test) at 50 mg/500 mg, 50 mg/850 mg, 50 mg/1,000 mg, 150 mg/500 mg, 150 mg/850 mg, or 150 mg/1,000 mg compared with co-administration of equivalent doses of single-component IR tablets (reference). Results: Across the six studies, a total of 64 to 83 participants were randomized to each treatment sequence and 57 to 68 were analyzed. The median tmax, mean t1/2, and mean plasma canagliflozin and metformin concentrationtime profiles were similar after administration of IR FDC and individual components.Bioequivalence criteria for the FDC with respect to AUC∞, AUClast, andCmaxof both canagliflozin and metformin met the 90% CI for the test-toreference geometric mean ratios of these parameters and were contained within the bioequivalence limits of 80% to 125%.Both treatments were well-tolerated with similar adverse events and the most common were gastrointestinal events generally attributed to metformin. Conclusions: When administered as IR FDC tablets or individual component IR tablets, the pharmacokinetics of canagliflozin and metformin across six dose levels were bioequivalent and were well-tolerated.