Studies in early clinical development
7. Thorough QT Study (TQT)
The QT interval is used as a measure of cardiac rhythm. It comes from the electrocardiography (ECG). The QT interval represents electrical depolarization (contraction) and repolarization (recovery) of the ventricles. A QT prolongation of more than 5 milliseconds in an electrocardiogram (ECG) is a (imperfect) biomarker which can be used to assess the risk that a medicine may provoke arrhythmia.
TQT studies are in vivo safety studies required for all new molecular entities (NMEs) and must take place prior to Phase III trials regardless of in vitro or non-clinical findings. TQT studies are typically conducted as single dose crossover studies with healthy participants. Researchers evaluate therapeutic and supratherapeutic (greater than therapeutic) doses of the medicine versus a positive control (for example commonly antibiotic moxifloxacin) and a negative control (placebo).
The ICH guidelines E14: ‘The Clinical Evaluation of QT/QTc Interval prolongation and Proarrhythmic Potential for Non-Antiarrhythmic medicines’ provide recommendations for the design, conduct, analysis, and interpretation of such clinical studies.
The information gained from TQT studies:
- To identify medicines that prolong QT, and therefore need a more thorough ECG monitoring in pivotal trials
- Labelling instructions accordingly