Effect of Food on the Pharmacokinetics and Pharmacodynamics of a Single Oral Dose of SHR4640, a Selective Urate Transporter 1 Inhibitor, in Healthy Chinese Male Volunteers

Abstract

SHR4640, also named as ruzinurad, is a selective human urate transporter 1 (URAT1) inhibitor developed for the treatment of hyperuricemia and gout. This study evaluated the high‐fat, high‐calorie food effect on the pharmacokinetics and pharmacodynamics of SHR4640 in healthy Chinese male volunteers. In this open‐label, randomized, 2‐period crossover phase 1 trial, 14 healthy male subjects were randomized to receive a single 10‐mg dose of SHR4640 under both fasted and fed conditions. The washout period was 7 days. Blood samples were collected for pharmacokinetic and pharmacodynamic analysis. Pharmacokinetic parameters were analyzed by a noncompartmental method. The safety of the drug was also evaluated in the trial. A total of 14 healthy male volunteers were enrolled in the study, and finally 13 healthy volunteers completed the study. A single 10‐mg dose of SHR4640 was safe and well tolerated in healthy Chinese male volunteers. After single‐dose administration of SHR4640, the 90%CIs of the geometric mean ratios of the area under the plasma concentration–time curve from time 0 to the last quantifiable concentration and the area under the plasma concentration–time curve from time 0 to infinity were within the equivalence criteria of 0.80‐1.25. The 90%CIs of maximum plasma concentration was slightly outside the lower limit of bioequivalent criteria, with about 13.40% decrease in the fed versus fasted condition. The time to maximum concentration was slightly delayed under the fasted condition. A single 10‐mg dose of SHR4640 was safe and well tolerated in this trial. The main pharmacokinetic parameters and serum uric acid lowering of SHR4640 were not affected by food effect; thus, SHR4640 can be recommended to be administered with or without food