Concentration QTc analysis of giredestrant: Overcoming QT/heart rate confounding in the presence of drug-induced heart rate changes.

ABSTRACT: Concentration-QTc (C-QTc) analysis has become a common approach for evaluating proarrhythmic risk and delayed cardiac repolarization of oncology drug candidates. Significant heart rate (HR) change has been associated with certain classes of oncology drugs and can result in over- or underestimation of the true QT prolongation risk. Because oncology early clinical trials typically lack a placebo control arm or time-matched, treatment-free baseline electrocardiogram collection, significant HR change brings additional challenges to C-QTc analysis in the oncology setting. In this work, a spline-based correction method (QTcSPL) was explored to mitigate the impact of HR changes in giredestrant C-QTc analysis. Giredestrant is a selective estrogen receptor degrader being developed for the treatment

SUBMITTER: Brooks L 

PROVIDER: S-EPMC10175970 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature