Assessment of a drug’s effects on cardiac repolarization has historically been performed using a by-timepoint evaluation of changes from baseline of the QTc interval, as described in the 2005 ICH E14 Guideline. In late 2015, the ICH E14 Questions & Answers document was revised again [ICH E14 Q&A (R3)3] to allow the use of concentration effect modeling as an alternative to a by-timepoint analysis. This potentially allows for the use of ECG and pharmacokinetic data collected in Phase I ascending dose studies to replace the data that was previously collected in a standard Thorough QT (TQT) study – but without requiring a large, dedicated cardiac safety trial. One year later, how has this regulatory change affected the strategy and execution of cardiac safety studies? Have Phase I QT assessments entirely superseded the TQT, or are there hidden complexities to the use of Phase I data to replace the TQT?
Join Dr. Robert Kleiman, Chief Medical Officer at ERT, for an informative 1-hour webinar to learn the practical lessons and best practices learned over the past year from protocols across multiple therapy areas. Dr. Kleiman will discuss the latest FDA clarifications about the study designs and statistical analyses that the FDA will accept in lieu of a standard TQT study. He will also explore how to optimize cardiac safety in your Phase I studies, potentially navigating around a standalone TQT and reducing your drug development investment by millions of dollars.