0期临床试验:新药临床研究的新模式  

Phase 0 clinical trial:a new way to successful clinical trial for candidate drugs

作　　者：张骏[1,2] 宋紫辉[1] 蔡永明[1] 刘昌孝[1] 张宗鹏[1] 

机构地区：[1]天津药物研究院天津市新药安全评价研究中心,天津300193 [2]天津医科大学药学院临床药学教研室天津市临床药物关键技术重点实验室,天津300071

出　　处：《首都医科大学学报》2011年第4期581-585,共5页Journal of Capital Medical University

基　　金：国家重点基础研究发展计划(973计划)项目专项(2010CB933900);"重大新药创制"科技重大专项(Z20082X09305-005)~~

摘　　要：0期临床试验是一种先于传统的Ⅰ期临床试验开展的研究,旨在评价受试药物的药效动力学和药代动力学特征。0期试验的特点是:小剂量、短周期、少量受试者、不以药物疗效评价为目的。0期试验主要用于作用靶点指标和(或)生物标记物的抗肿瘤候选药物的药效学和药动学评价。一般可将0期临床研究的类型分为3类。开展0期临床研究可参考美国食品与药品监督管理局的"探索性研究药物指南"。0期临床试验的局限性可以通过良好的试验设计加以克服。对于分子靶向的抗癌药物,0期临床研究可提高研究效率和后续研究的成功率。Phase 0 trials are designed primarily to evaluate the pharmacodynamic and/or pharmacokinetic properties of selected investigational agents before initiating traditional phase I testing.In a phase 0 trial,the pharmacodynamic effects of an investigational agent are evaluated by a target or biomarker which is measured by an assay established and validated in preclinical models.The phase 0 trial is characterized by a small number of patients enrolled and limited dosing period with a non-therapy-intended dose range.Furthermore,phase 0 trials are classified into three types and conducted under the US Food and Drug Administration exploratory investigational new drug guidance with less preclinical toxicity data than usually required for traditional first-in-human studies.A well designed and executed phase 0 trial can overcome its limitations and has a great potential for improving the efficiency and success of subsequent trials,particularly those evaluating molecularly targeted antitumor candidates.

关 键 词：0期临床试验 靶点 生物标记物 探索性研究药物 药代动力学 药效学 

分 类 号：R969[医药卫生—药理学]