PDF(Pubmed)
Abstract：
HRS9432(A) is a long-acting echinocandin antifungal medication primarily used to treat invasive fungal infections, particularly invasive candidiasis. The safety, tolerability, and pharmacokinetic characteristics of HRS9432(A) injection were investigated in a randomized, double-blind, placebo-controlled, single- and multiple-ascending-dose Phase I study involving 56 healthy adult subjects. Doses ranging from 200 to 1200 mg were administered. Safety was continually monitored, including adverse events, clinical laboratory examinations, vital signs, 12-lead electrocardiograms, and physical examinations, while the pharmacokinetic profile within the body was evaluated. The results indicated that concentrations of HRS9432 peaked immediately after infusion, demonstrating essentially linear pharmacokinetic characteristics within the dosage range of 200-1,200 mg. It exhibited a low clearance rate and an extended half-life, with a clearance of approximately 0.2 L/h, a volume of distribution of around 40 L, and a half-life of approximately 140h following a single dose. The accumulation index for AUC0-τ after multiple doses ranged from 1.41 to 1.75. No severe adverse events occurred during the study, and the severity of all adverse events was mild or moderate. Therefore, the intravenous administration of HRS9432(A) in healthy Chinese adult subjects, either as multiple infusions of 200 to 600 mg (once a week, four doses) or as a single infusion of 900-1,200 mg, demonstrated overall good safety and tolerability. The pharmacokinetic exhibited essentially linear characteristics in the body, supporting a weekly dosing frequency for clinical applications and providing additional options for the treatment or prevention of invasive fungal infections.
RESULTS: This study is registered with the International Clinical Trials Registry Platform as ChiCTR2300073525.
RESULTS: This study is registered with the International Clinical Trials Registry Platform as ChiCTR2300073525.
摘要：
HRS9432（A）是一种长效棘白菌素抗真菌药物，主要用于治疗侵袭性真菌感染，特别是侵袭性念珠菌病。安全,耐受性,HRS9432（A）注射液的药代动力学特征进行了随机研究，双盲,安慰剂对照,单剂量和多剂量递增I期研究，涉及56名健康成人受试者。施用200至1200mg的剂量。持续监测安全性，包括不良事件，临床实验室检查，生命体征,12导联心电图,和身体检查，同时评估了体内的药代动力学特征。结果表明，HRS9432的浓度在输注后立即达到峰值，在200-1,200mg的剂量范围内证明了基本上线性的药代动力学特征。它表现出低清除率和延长的半衰期，间隙约为0.2L/h，大约40升的分布体积，单剂量后的半衰期约为140h。多次剂量后AUC0-τ的累积指数范围为1.41至1.75。研究期间未发生严重不良事件,所有不良事件的严重程度均为轻度或中度。因此,HRS9432（A）在中国健康成人受试者中的静脉给药，或者作为200至600毫克的多次输注(每周一次，四个剂量)或作为900-1,200毫克的单次输注，显示总体良好的安全性和耐受性。药代动力学在体内表现出基本上线性的特征，支持临床应用的每周给药频率，并为治疗或预防侵袭性真菌感染提供其他选择。
结果：本研究在国际临床试验注册平台注册为ChiCTR2300073525。
结果：本研究在国际临床试验注册平台注册为ChiCTR2300073525。
