All Times EDT
Keywords: QT Prolongation, C-QTc, TQT
QT prolongation is a measure of delayed ventricular repolarization that can lead to dangerous cardiac arrhythmias, Torsades de Pointes (TdP), and sudden death. Recognizing a wide array of medications that may induce QT prolongation, ICH issued the E14 guideline in 2005 which codified the need for clinical evaluation and the Thorough QT/QTc (TQT) study – a rigorous and costly analysis to assess if a new drug has an increased risk for QT prolongation.
Since adoption of ICH E14, use of modeling and simulation techniques have gained attention as an alternative to the full TQT study. ICH revised the E14 guideline in 2015 and allow Concentration-QTc (C-QTc) modeling as the primary analysis. The C-QTc approach has a number of advantages and can eliminate the need for a TQT study.
Questions: • How many studies have you been involved in using C-QTc modeling? • What types of assumptions and what if some assumptions are not satisfactory? • What are the final models? • What are the successes of C-QTc modeling in regulatory submission? • How to proceed if the results are outside of the regulatory thresholds?
In the roundtable discussion, let's share experiences in using C-QTc modeling to assess QT interval prolongation.