PII-130 - PHARMACOKINETIC EVALUATIONS TO COMPARE FIXED-DOSE OF ENAVOGLIFLOZIN/GEMIGLIPIN 0.3/50 MG AND THE CORRESPONDING LOOSE-DOSE COMBINATION, AND TO ASSESS FOOD EFFECTS ON ENAVOGLIFLOZIN IN HEALTHY SUBJECTS.

S. Park¹, J. Hwang¹, S. Jeong¹, Y. Choi¹, J. Cho², Y. Jeong², J. Nah², M. Park¹; ¹Chung-buk National University College of Medicine and Hospital, ²Daewoong Pharmaceutical Co., Ltd..

Background: Envlo® (enavogliflozin 0.3 mg/tab) is a novel sodium-glucose cotransporter-2 inhibitor and has received regulatory approval in South Korea for type 2 diabetes treatment in 2023. This study compared the pharmacokinetic (PK) profiles of fixed-dose and loose-dose combinations (FDC and LDC, respectively) of enavogliflozin 0.3 mg and gemigliptin 50 mg in healthy subjects. Moreover, a separate study explored food effects (FE) on enavogliflozin.

Methods: Two independent clinical trials (Study I and II) were conducted using an identical randomized, open-label, oral, single-dose, two-sequence, two-period crossover design. In Study I, 38 subjects orally received FDC or LDC of enavogliflozin 0.3 mg and gemigliptin 50 mg during each period. In Study II, 30 subjects were administered enavogliflozin 0.3 mg either while fasting or after the high-fat meal in each period. Blood samples for the plasma enavogliflozin and gemigliptin analysis were collected up to 72 hours post-dose. PK parameters were estimated using noncompartmental analysis.

Results: The geometric mean ratios [90% confidence interval] (GMR [90% CI]) of FDC compared to LDC for the maximum plasma concentrations (Cmax) and the area under the concentration-time curves (AUC0-t) of enavogliflozin were 1.0521 [0.9950-1.1126] and 1.0812 [1.0430-1.1208], respectively, and the corresponding values of gemigliptin were 1.0005 [0.9472 - 1.0569] and 1.0152 [0.9900 – 1.0410], respectively. Overall, all GMR [90% CI] of the PK parameters of enavogliflozin and gemigliptin fell within the bioequivalence criteria of 0.8–1.25. After a high-fat meal was provided, the median Tmax (the time to reach Cmax) of enavogliflozin was prolonged from 1.25 to 2.00 hours, and the Cmax was decreased by approximately 17 % compared to the fasted state. Meanwhile, the AUC0-t was similar between the fed and fasted states (GMR [90% CIs]: 0.9014 [0.8706–0.9332]).

Conclusion: The FDC of enavogliflozin 0.3 mg and gemigliptin 50 mg can be used as an alternative to their loose combination. A high-fat meal delayed the enavogliflozin absorption, but its absorption extent was unaffected. Considering the previous report that the efficacy of enavogliflozin was related to its AUC, enavogliflozin could be administered orally with or without food.