Keywords: TQT, C-QTc, single-ascending dose studies, multiple-ascending dose studies
Thorough QT (TQT) studies are considered as expensive and their corresponding statistical analysis methodology, based on the ICH E14 guidance, has been criticized as too conservative in some publications. The ICH E14 Q&A (R3), released in December, 2015, states that concentration-QTc (C-QTc) analysis with all available data across all doses to characterize the potential for a drug to influence QTc, can serve as an alternative for decisions to classify the risk of a drug. The concentration-QTc data could come from first-in-human single-ascending dose (SAD) studies, multiple-ascending dose (MAD) studies, or other studies. This presentation will investigate how well the drug concentration effect on QTc prolongation in various C-QTc models can be captured by combining a SAD study and a MAD study, comparing to use a SAD study only.
