生物学的同等性とバイオアベイラビリティのジャーナル

概要

Bioequivalence of Canagliflozin/Metformin Immediate Release Fixed- Dose Combination Tablets Compared with Concomitant Administration of Single Components of Canagliflozin and Metformin in Healthy Fed Participants

Devineni D, Curtin CR, Ariyawansa J, Weiner S, Stieltjes H, Vaccaro N, Shalayda K, Murphy J, DiProspero NA and Wajs E

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.