目的 探讨在Ⅰ期临床试验中加强心电监测的策略,为全面QT/QTc研究(Thorough QT/QTc Study,TQT/QTc)的必要性及新药后续开发策略提供参考。方法 参考国内外心脏安全性研究的相关进展,结合全面QT/QTc研究指南,探讨本研究策略。结果 本文提出并探讨了Ⅰ期试验中加强心电监测的适用范围,分析并阐述方案设计及质量控制的原则与规范。结论 新药Ⅰ期临床试验中加强心电监测是依托Ⅰ期临床试验的平台对心脏安全性所进行的初步评价与筛选,在不增加受试者药物暴露的情况下获取及挖掘更多安全性信息,为进一步QT/QTc试验提供依据和参考。
Abstract
OBJECTIVE To discuss the strategy of strengthening ECG monitoring in phase I study and to provide references for the necessity of thorough QT/QTc study and for the subsequent development strategies. METHODS Relevant progresses in cardiac safety studies and guidelines of QT/QTc study were referred to in discussing the study strategy. RESULTS The applicable scope, protocol design and quality control of the strengthening ECG monitoring study have been preliminarily explored. CONCLUSIONS Based on the phase I clinical trials,cardiac safety of the new drugs is preliminarily evaluated and screened,without increasing drug exposure, and this study during phase I clinical trial will provide basis and reference for the further QT/QTc trial.
关键词
Ⅰ期临床试验 /
心电监测 /
QT/QTc研究
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Key words
:phase I clinical trial /
ECG monitoring /
QT/QTc study
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中图分类号：
R969.3
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参考文献
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BORJEED, CHRISTINE G, CHARLES T B,et al. Cardiac safety research consortium: Can thethorough QT/QTc study be replaced by earlyQT assessment in routine clinicalpharmacology studies? Scientific update anda research proposal for a path forward. Am Heart J, 2014, 168(3): 262-272.
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脚注
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基金
国家科技部十二五重大新药创制-心脑血管疾病新药临床评价技术平台研究课题资助项目(2012ZX09303-008-002)
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