QT

Thorough QT trials

Propensity to cause QT prolongation as lead to the removal from the market of several blockbuster drugs, including at least one world-leading product. QT prolongation carries a risk of ‘torsade de pointes’ and other types of ventricular tachycardia, which may progress to ventricular fibrillation and death. Every new small molecule has to be tested in various ways to ensure that it’s unlikely to prolong QT interval, and the gold standard in this field is the thorough QT trial.

Thorough QT trials require repeated administration of supratherapeutic doses of IMP to healthy volunteers. The trials must include placebo and positive-control treatment arms. Serial 12-lead ECGs are recorded, and QT interval measured – typically using an automated method followed by expert ‘manual’ overread. The utmost care is needed to ensure the highest quality of ECG recording, to exclude the possibility of false negative results.