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
- *Corresponding Author:
- Damayanthi Devineni
Janssen Research and Development, LLC
920 Route 202, Raritan, NJ 08869, USA
Tel: (908) 927-4217
Fax: (908) 927-2573
E-mail: [email protected]
Received Date: July 08, 2014; Accepted Date: September 30, 2014; Published Date: October 11, 2014
Citation: Devineni D, Curtin CR, Ariyawansa J, Weiner S, Stieltjes H, et al. (2014) 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. J Bioequiv Availab 6: 164-173. doi: 10.4172/jbb.1000199
Copyright: © 2014 Devineni D, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.