The pharmacokinetics, pharmacodynamics and tolerability of SHR6508 in chinese healthy subjects: a randomized, placebo-controlled, double-blind, single-dose and dose-escalation phase I trial.

Abstract

This study aimed to evaluate the pharmacokinetics (PK), pharmacodynamics (PD), safety, and tolerability of SHR6508 injection, a new calcimimetic agent, in healthy Chinese subjects following single dose. This study utilized a placebo-controlled, single-dose, and dose-escalation design with four dose groups (0.5 mg, 2.5 mg, 5 mg, 10 mg). The trial started with a low dose and continuing to the next dose after completion of the out-of-group safety assessment of the previous dose group. Blood samples were collected at 15 time points to measure pharmacokinetic and pharmacodynamic parameters. Safety was assessed by therapeutic emergency adverse events (TEAEs), clinical laboratory tests, vital signs, electrocardiograms (ECGs), and physical examination. Of the 22 subjects who completed this study, 16 received SHR6508 Injection and 6 received placebo. In the 0.5-5 mg group, t_1/2z was 8.8 h-28.3 h. C_max and AUC increased proportionally with dose. PD results showed that SHR6508 dose dependently decreased iPTH and blood calcium levels in subjects in the 0.5-5-mg dose range; blood phosphorus levels in subjects in the 5 mg group tended to be elevated compared to those in the placebo group. Twenty-one TEAEs occurred in 12 subjects (54.5%), and no serious or severe TEAEs occurred. The overall safety and tolerability of a single intravenous dose of 0.5-5 mg SHR6508 in healthy subjects was favorable, exhibiting dose-dependent PK and PD properties.