背景:HY0721是一种用于治疗急性缺血性卒中的新型磺酰脲受体1-瞬时受体电位美司他丁4(SUR1-TRPM4)抑制剂。本研究旨在评估安全性,耐受性,在中国健康受试者中单次和多次静脉施用HY0721的药代动力学(PK)谱。
方法:该研究招募了48名和30名健康志愿者,分别为单次递增剂量(SAD)队列(20、60、120、240和320mg)和多次递增剂量(MAD)队列(60、120和160mg/bid),分别,接受相应剂量的HY0721或安慰剂。安全性监测包括但不限于记录不良事件(AE),生命体征,心电图,和实验室测试。从受试者收集血液样品以确定用于PK评估的HY0721的浓度。
结果:在SAD研究中,HY0721的给药显示出良好的安全性和耐受性,高达320mg,在MAD研究中,高达160mg每天两次。最常见的AE是注射部位反应,并且没有AE导致停药或受试者退出。在SAD研究中,在20至320mg的剂量下,HY0721的暴露增加大于剂量成比例的方式。在每天两次60至160mg的多剂量后观察到线性PK曲线,没有积累的证据。此外,HY0721的人有效剂量估计为120mg。
结论:这项研究表明,在中国健康受试者中,静脉内给药HY0721是安全且耐受性良好的,并提供60至160mgb.i.d.作为进一步临床试验的推荐剂量范围。
背景:中国药物试验。Org.cn;不.CTR20202604,2020年12月18日。
BACKGROUND: HY0721 is a novel inhibitor of sulfonylurea receptor 1-transient receptor potential melastatin 4 (SUR1-TRPM4) for the treatment of acute ischemic stroke. This study aimed to evaluate the safety, tolerability, and pharmacokinetic (PK) profiles of single and multiple intravenous administration of HY0721 in Chinese healthy subjects.
METHODS: The study enrolled 48 and 30 healthy volunteers in the single-ascending dose (SAD) cohort (20, 60, 120, 240, and 320 mg) and multiple-ascending dose (MAD) cohort (60, 120, and 160 mg/bid), respectively, to receive the corresponding dosage of HY0721 or placebo. Safety monitoring included but was not limited to recording adverse events (AEs), vital signs, electrocardiograms, and laboratory tests. The blood samples were collected from subjects to determine the concentrations of HY0721 for PK evaluation.
RESULTS: The administration of HY0721 showed good safety and tolerability up to 320 mg in the SAD study and up to 160 mg twice daily in the MAD study. The most common AE was injection site reaction, and no AE led to discontinuation of administration or subject dropout. The exposures of HY0721 increased greater than dose proportional manner at the dosages of 20 to 320 mg in the SAD study. A linear PK profile was observed following multiple doses ranging from 60 to 160 mg twice daily, with no evidence of accumulation. Additionally, the human effective dose of HY0721 was estimated to be 120 mg.
CONCLUSIONS: This study demonstrated the intravenous administration of HY0721 is safe and well-tolerated in Chinese healthy subjects and provided 60 to 160 mg b.i.d. as the recommended dosing range for further clinical trials.
BACKGROUND: ChinaDrugTrials.Org.cn; No. CTR20202604, 18 December 2020.