Galapagos B.V., Leiden, The Netherlands.
Galapagos NV, Mechelen, Belgium.
Clin Pharmacol Ther. 2023 Feb;113(2):310-320. doi: 10.1002/cpt.2596. Epub 2022 Apr 27.
During development of a drug, the requirement of evaluating the proarrhythmic risk and delayed repolarization needs to be fulfilled. Would it be possible to create an alternative to a thorough QT (TQT) study or is there a need to perform a dedicated TQT study? How is an alternative approach generated, what information is available, and which instructions are considered missing today to generate such an approach? This tutorial describes the considerations and path followed to create an early and feasible alternative to a TQT study using experience-based insights from a successful application to the US Food and Drug Administration for GLPG1972, an ADAMTS-5 inhibitor, and discusses the approach used in light of the current guidelines and literature.
在药物开发过程中，需要评估致心律失常风险和延迟复极。是否有可能创建一种替代全面 QT（TQT）研究的方法，或者是否需要进行专门的 TQT 研究？如何生成替代方法，有哪些信息可用，以及目前生成这种方法时认为缺少哪些说明？本教程介绍了考虑因素和创建 TQT 研究的早期且可行的替代方法的途径，该方法是基于 GLPG1972（一种 ADAMTS-5 抑制剂）成功应用于美国食品和药物管理局的经验性见解，同时根据当前指南和文献讨论了所使用的方法。
