TL53: QT/QTc Evaluation in Early Development Studies
*Jaya Natarajan, Janssen R&D 


As per ICH E14 guidance, a thorough QT (TQT) study to evaluate a drug’s potential to prolong QT/QTc intervals is required for every new drug application. If QT/QTc prolongation is observed in early development (ED) studies, the sponsor may be able to obtain a waiver for the TQT study, provided the information is properly incorporated in the labeling. Research is ongoing on how ED studies can be utilized, instead of a TQT study, to evaluate QT prolongation and proarrhythmic potential. The topics of interest for this discussion are: (1) How extensive are the ECG measurements in ED studies by various sponsors? (2) Appropriate study designs for ED studies to evaluate QT prolongation (3) Establishing assay sensitivity in ED studies in the absence of a positive control (4) Appropriate analysis methodologies (5) What would be required to convince the regulatory agencies to waive TQT study.