PII-113 - EFFECTS OF RENAL FUNCTION AND FOOD ON PHARMACOKINETIC AND PHARMACODYNAMIC CHARACTERISTICS OF EPAMINURAD.

S. Park¹, J. Hwang¹, S. Jeong¹, Y. Choi¹, H. Choi², S. Cho², D. Cho³, M. Park¹; ¹Chung-buk National University College of Medicine and Hospital, ²Ajou University School of Medicine, ³JW Pharmaceutical Co., Ltd..

Background: Epaminurad is a novel selective human uric acid transporter 1 inhibitor under development for treating gout caused by hyperuricemia. In the previous phase 1 study, tolerability of epaminurad was confirmed for up to 10 mg of multiple oral doses in healthy participants. The phase 2a clinical trial with daily doses ranging from 0.25 to 10 mg confirmed a dose-dependent decrease in serum uric acid levels. The 6 and 9 mg dose of epaminurad is under the phase 3 to compare and evaluate its efficacy and safety with febuxostat in gout patients. In this study, we performed a clinical trial to achieve two objectives: to identify the effects of renal function and the food on the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of epaminurad 9 mg.

Methods: An open-label, oral, single-dose trial was conducted in the following groups: group 1, normal renal function, group 2/3, moderate 1/2 renal impairment. Group 1 orally received epaminurad 9 mg in a two-way crossover study under both fasted and fed conditions, and groups 2 and 3 received epaminurad 9 mg once during the fasting state. Serial blood samples and timed urine samples were collected to analyze plasma epaminurad and fractional excretion of uric acid (FEUA), the ratio of uric acid clearance to creatinine clearance.

Results: A total of 27 subjects (12, 9, and 6 subjects in groups 1-3, respectively) completed the study as planned. In group 2, the maximum plasma concentration (Cmax) and the area under the curve (AUC0-t) of epaminurad decreased by approximately 8 % and 16 %, respectively, compared to group 1. On the other hand, in group 3, Cmax and AUC0-t increased by approximately 3 % and 2 %, respectively, compared to group 1. As for PD, the 0-72h FEUA was increased by about 11 % and 34 % in groups 2 and 3, compared to group 1, respectively.
After a high-fat meal, the median Tmax of epaminurad was prolonged from 1.00 to 3.00 hours, and the Cmax was decreased by approximately 12 %, compared to the fasting state. The AUC0-t was similar between the fed and fasting states. Although the FEUA was increased by approximately 17 % in the fed state compared to the fasting state, it is considered due to the purine in the high-fat meal.

Conclusion: There was no significant difference between normal and moderate renal impaired groups regarding PK and PD of epaminurad. Also, significant food effects were not observed for epaminurad.