Lessons Learned From Hundreds of Thorough QT Studies

Conclusions: In exploring whether a thorough QT (TQT) study may be needed, we recommend that the relationship analysis between QTc and drug plasma concentration be performed when proper single ascending dose (SAD) and multiple ascending dose (MAD) studies are available. If the relationship cannot be detected and the 90% upper confidence interval at a fixed concentration level (50th or 75th percentile, or mean peak plasma concentration [Cmax]) is below a certain threshold level (eg, 10 milliseconds), then a TQT study might be unnecessary. If the relationship can be established and the 90% lower confidence interval at a fixed concentration level (eg, mean Cmax) is greater than 10 milliseconds, further investigation is needed. If the signal is real, one might choose intensive safety monitoring during later drug development instead of a TQT study for a good compound. However, there are still some gray areas in which this analysis alone cannot determine the potential QT liability of the drug, and a TQT type of study might be worth considering.
Source: Therapeutic Innovation and Regulatory Science - Category: Drugs & Pharmacology Authors: Tags: Product Safety Source Type: research