The pharmacokinetics, pharmacodynamics and tolerability of SHR6508 in Chinese healthy subjects

Abstract

Background Secondary hyperparathyroidism (SHPT) mainly occurs in patients with chronic renal failure. SHR6508 is a new type of calcimimetic molecule, intended for patients with SHPT who are undergoing maintenance hemodialysis for chronic kidney disease. This study aimed to evaluate the pharmacokinetics (PK), pharmacodynamics (PD), safety, and tolerability of a new calcimimetic agent, SHR6508 injection, in healthy Chinese subjects. Methods In this phase I study, healthy subjects were administered SHR6508 injection via intravenous infusion according to a randomization table on the morning of the first day after admission. Blood samples were collected at 15 time points to measure the pharmacokinetic (PK) and pharmacodynamic (PD) parameters of SHR6508. Adverse events that occurred during administration were also evaluated. Results 23 subjects were successfully screened and enrolled in the study. Except for 1 subject who withdrew from the study before medication, the remaining 22 subjects completed the study. No serious adverse events or adverse events leading to death occurred. The blood drug concentration of SHR6508 injection in healthy subjects reached its peak rapidly after a single intravenous dose. With the exception of the low-dose group, there was no significant difference in the distribution and elimination-related parameters Vz, t1/2z, and CLz between the other dose groups. The plasma drug exposure level (Cmax and AUC) of SHR6508 increased proportionally with the dose, and it showed linear pharmacokinetic characteristics within the dose range of 0.5-5 mg. The results of variance analysis showed no significant difference in PK characteristics between different genders. Conclusion After a single intravenous injection of 0.5-5 mg of SHR6508 injection in healthy subjects, the iPTH and blood calcium levels in the body decreased, and this effect showed dose-dependent characteristics, which is consistent with the expected effect of this product. The overall safety and tolerability of SHR6508 injection in healthy subjects after a single intravenous dose of 0.5-5 mg was good. Trial Registration: The trial is registered at chinadrugtrials.org.cn (ChiCTR2100048905)(19/07/2021).