Bioequivalence and safety assessment of test vs. reference canagliflozin tablets in healthy Chinese volunteers: a randomized, open-label, single-dose, two-sequence, two-period crossover study under fasting and fed states

Abstract Background: Diabetes Mellitus Type 2 is a disease that is becoming increasingly challenging in global public health. Due to their cardiorenal protective benefits, SGLT2 inhibitors, a class of antidiabetic medications, are currently a vital treatment for type 2 diabetes. In this study, healthy Chinese volunteers subjected to feeding or fasting were assessed on the safety and bioequivalency of 100 mg test formulation of canagliflozin tablet in relation to the reference innovator 100 mg tablet formulation. Methods: An open label, randomized, two-period crossover study with a washout period of seven days was used to reduce any carry-over effect from the drugs administered. Fifty-six subjects who met all the inclusion and exclusion criteria were enrolled and delineated into two groups, i.e., the fed group and the fasting group. To determine the drug concentration after a single oral administration of 100 mg, plasma was obtained from individuals administered the reference and test drugs. To quantify canagliflozin in the plasma, a validated HPLC-MS/MS technique was utilized. Key pharmacokinetic characteristics were studied through plasma concentration versus time analysis. All participants in the two groups (28 per group) completed the study. Results: The primary pharmacokinetic parameters of the test formulation were statistically analyzed and found to be equivalent to the reference formulation, meeting all regulatory bioequivalency requirements. In the case of Cmax, AUC0-t, and AUC0-∞ geometric mean ratios, all the 90% confidence intervals were within the expected bioequivalence limits of 80.00% to 125.00%. Moreover, it was noted that there was a similarity in the safety and tolerance aspects between the two formulations among the subjects in the study. Conclusion: Overall, results from this trial provide proof of bioequivalence of the test canagliflozin product with the innovator product in healthy Chinese subjects under both fasting and fed conditions. The results support the clinical equivalence of both preparations, and the test formulation is a reliable alternative for clinical use. Trial registration: This trial was registered on the China Drug Trials registry (http://www.chinadrugtrials.org.cn) on June 13, 2022 (registration number: CTR20221376), and retrospectively registered on the Chinese Clinical Trial Registry (ChiCTR; http://www.chictr.org.cn) on September 29, 2026 (registration number: ChiCTR2600133557). Human Ethics and Consent to Participate declarations: The Independent Ethics Committee at Panyu Central Hospital in Guangzhou City, Guangdong Province, China, approved the study protocol (Approval No. PYZXYYEC [2022-06]-01). All healthy volunteers provided written informed consent to participate in the study prior to its registration.