The pharmacokinetics, Pharmacodynamics and Tolerability of SHR6508 in
Chinese Healthy Subjects : A
Randomized,Placebo-Controlled,Single-dose and Dose-Escalation Phase Ⅰ
trial
Abstract
Purpose: 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. Methods: 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.
Results: Of the 22 subjects who completed this study, 16 received
SHR6508 Injection and 6 received placebo. In the 0.5-5 mg group Tmax was
0.033 - 0.058 h, and t1/2z was 8.8 h-28.3 h. Cmax 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. 21
TEAEs occurred in 12 subjects (54.5%), and no serious or severe TEAE
occurred. Conclusion: 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.