Assessment of moxifloxacin-induced QTc prolongation in canine and nonhuman primate using a linear mixed effect modeling approach

SPS 2023 -- Recent introduction of the ICH E14/S7B Q&As has increased the opportunity to perform clinical QTc characterization during Phase I in place of a thorough QT (TQT) study and improve product QTc labeling in situations where a compound is negative in both the in vitro hERG and in vivo QTc assays. To take advantage of this new guidance, especially in the case of E14 Q&A 6.1, the in vivo QT assay must be powered to detect an effect similar to that of a human TQT study and take interspecies QTc differences into account. Conduct of concentration-QTc (cQTc) modeling of large animal data can improve study power over that of a traditional by-time analysis. Moreover, cQTc analysis can be used to quantify the drug concentration required to induce a QTc effect at a target threshold (e.g., 10 msec) in a large animal species versus human to determine any species shift, as required by the new guidance. To prepare for this new guidance, we tested the effects of moxifloxacin on the QTc interval in canine and nonhuman primate (NHP) to investigate study sensitivity and human translation using the new best practice methodologies.

Copy and paste this URL:

https://biopharma.labcorp.com/latest-thinking/explore-library/detail.html/covance/assetLibrary/posters/PoppSPS23-Moxi-induced-QTc.jpg