Pharmacokinetics and Safety of HRS-1780 in Renal Impaired Subjects: A Multicenter, Non-Randomized, Open-Label Study

HRS-1780 is a selective non-steroidal mineralocorticoid receptor antagonist developed for the treatment of chronic kidney disease. This study aimed to assess the pharmacokinetics (PK) and safety profiles of HRS-1780 in subjects with renal impairment.

Eligible participants were enrolled in the healthy (glomerular filtration rate [GFR] of ≥90 mL/min), mild (GFR of 60-89 mL/min), and moderate renal impairment (GFR of 30-59 mL/min) groups with 9 subjects each and orally received 20 mg HRS-1780. Concentrations of HRS-1780 and its main metabolites were measured in plasma and urine. PK profiles between healthy and renal impairment subjects were compared using analysis of variance.

A total of 27 subjects completed the study. HRS-1780 was rapidly absorbed and eliminated, with T_max of 0.50-0.52 hour and t_1/2 of 2.06-2.56 hours. Exposure (AUC_0-inf) to HRS-1780 was comparable between mildly and moderately renal impaired subjects, while higher, but not significantly than that in healthy subjects. Similar plasma protein binding among different renal function groups suggested a consistent effect of renal function on total and unbound HRS-1780. Renal clearance of HRS-1780 decreased with severity of renal impairment, but renal elimination of HRS-1780 was minimal. Exposure to SX2183-M3 was significantly increased in the moderate renal impairment subjects. Renal impairment did not appear to be associated with an increased risk of adverse events.

HRS-1780 PK and safety profiles did not differ significantly between healthy and renal impairment subjects. This supports the drug dose regimen for renal impairment patients in clinical practice.