It is possible to get an accurate baseline QT measurement, while taking the increased heart rate into account. One solution we have implemented is including exercise as part of the baseline ECG collection.

In our experience conducting thorough QT studies, the use of treadmills can mimic the increased heart rate levels that the compound is known to cause. An example of a possible study design incorporating a treadmill includes:

·         Conducting a baseline treadmill test the day before initial dosing to cover the range of heart rate anticipated while on the study drug. Baseline data are amassed a day before to avoid variations associated with data collection at a different part of the day.

·         Setting a goal of achieving the same heart rate in all participants during the treadmill test. If the anticipated heart rate on the study product is 90 to 100bpm, the goal of the treadmill test is to achieve the same heart rate in all of the subjects. Once the heart rate of more than 100bpm is achieved, the test stops.

·         Collecting consistent and reliable data that will be used in the analysis with an H-12 ECG. The core lab will also extract triplicate ECGs for a range of more than 80 to 90bpm and a range of more than 90 to 100bpm.

·         Calculating the subject-specific QTc1 with that data.This will be used when evaluating the QT data while on the study product.

·         Performing a trial run in a small group of participants is recommended to ensure the quality of the data collected.

This approach provides more accurate correction factors, and thus better data for evaluating the real-world applications of a compound as the regulatory process moves forward.