PI-045 - COMPARATIVE PHARMACOKINETICS BETWEEN DA-2811, A DAPAGLIFLOZIN PRODRUG FORMULATION, AND CONVENTIONAL DAPAGLIFLOZIN TABLET.

J. Koh¹, E. Yang¹, H. Kim¹, J. Oh², S. Yoon¹, J. Chung¹; ¹Seoul National University Bundang Hospital, Seoul, Republic of Korea, ²Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea.

Background: Dapagliflozin is a widely used sodium-glucose cotransporter 2 (SGLT-2) inhibitor class oral hypoglycemic drug, but it is unstable due to its amorphous structure. DA-2811 is a novel prodrug formulation developed to improve the pharmaceutical processability and stability of dapagliflozin. This study aimed to compare the pharmacokinetics (PKs) between the DA-2811 and the conventional dapagliflozin tablet (Forxiga®, reference drug).

Methods: An open-label, randomized, two-treatment, two-way crossover study was conducted in healthy subjects. Subjects received a single 10mg oral dose of DA-2811 or reference drug in each period with at least a 7-day washout. Serial blood samples for PK analysis were collected up to 48 hours post-dose. The PK parameters of dapagliflozin were calculated by a noncompartmental method. The geometric mean ratios (GMRs) and its 90% confidence intervals (CIs) of DA-2811 to reference drug for maximum plasma concentration (Cmax) and area under the plasma concentration-time curve from zero to the last measurable point (AUClast) were estimated. The PK of unchanged DA-2811 was also explored.

Results: A total of 30 subjects were randomized, and 28 subjects completed the study as planned. The PK profiles of dapagliflozin were comparable between the two treatments. The GMRs (90% CIs) of Cmax and AUClast were 0.98 (0.86 – 1.10) and 0.98 (0.94 – 1.02), respectively, and both were within the pharmacokinetic equivalence range of 0.80 – 1.25. The systemic exposure of unchanged DA-2811 was negligible, which suggests the rapid conversion to dapagliflozin.

Conclusion: DA-2811 showed equivalent pharmacokinetic properties to Forxiga®, and it indicates that DA-2811 can become an alternative treatment option to the conventional dapagliflozin tablet.