Brazil China Japan RussiaSpain

CiPA and the New Cardiotoxicity Paradigm Part 4: Clinical Translation

In order for the efforts of the Ion Channel, Myocyte and In Silico Working Groups to be relevant to the clinical situation, a realistic cross-section of compounds had to be selected for evaluation. This task fell to the Clinical Translational Working Group. This Working Group selected compounds based multiple types of electrophysiological risks including; torsadogenic potential, ion channel modification and blockage and non-hERG Torsade de Pointes (TdP) risk. The compounds chosen had known risk factors, published in the FDA AERS database and other sources, and were categorised as very low, intermediate and high risk as appropriate.

The other key issue the Clinical Translation Working Group must address is creating and standardising assessment of human ECGs in Phase I clinical trials. In the clinic, evaluation of electrophysiological effects either not examined or anticipated in nonclinical testing, such as sophisticated T-wave analysis, will be studied in addition to QTc analysis. As development continues into human test subjects and towards regulatory scrutiny, it is critical that this approach to ECG assessment be well defined.

Part 1: Overview
Part 2: Platforms – Microelectrode Array and Voltage Sensing Optics

Part 3: In Silico Prediction