Concentration-QTc modeling provides consistent high QTc sensitivity across species and study designs

SPS 2025 -- To support an integrated risk assessment for QTc prolongation under the ICH E14/S7B Q&As, the in vivo QTc assay should follow best practice for demonstrating high drug exposure multiples and sufficient QTc detection sensitivity. Concentration-QTc (C-QTc) modeling can improve study power compared with a traditional by-time analysis and can be used to quantify drug concentration producing a 10 msec effect and any shift between human and preclinical species. The objective was to compare by-time analysis and concentration-QTc modeling sensitivity in dog, nonhuman primate (NHP) and minipig.