Best practice considerations for nonclinical in vivo cardiovascular telemetry studies in non-rodent species: Delivering high quality QTc data to support ICH E14/S7B Q&As

• Published in: Journal of pharmacological and toxicological methods Vol. 123; p. 107270
• Main Authors: Rossman, Eric I., Wisialowski, Todd A., Vargas, Hugo M., Valentin, Jean-Pierre, Rolf, Michael G., Roche, Brian M., Riley, Steve, Pugsley, Michael K., Nichols, Jill, Li, Dingzhou, Leishman, Derek J., Kleiman, Robert B., Greiter-Wilke, Andrea, Gintant, Gary A., Engwall, Michael J., Delaunois, Annie, Authier, Simon
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2023
• Subjects: Cardiovascular safety; drug development; drugs; guidelines; hERG; ICH E14; ICH E14/S7B Q&as; ICH S7B; In vivo cardiovascular telemetry; industry; Integrated risk assessment; pharmacokinetics; QT prolongation; species; telemetry; Ventricular repolarization; RR; CRO; TdP; FDA; CNS; LOEL; HR; MDD; NOEL; ICH S7B; Integrated risk assessment; AUC; In vivo cardiovascular telemetry; IKs; ANCOVA; IKr; 3Rs; Ventricular repolarization; ANOVA; IACF; LSD; Cmax; QTc; hERG; Q&As; QT; Cardiovascular safety; FIH; NME; ICH E14/S7B Q&as; ECG; RMSE; IV; SEND; ICH; NCE; C-QT; QT prolongation; CV; PC; PD; TQT; ICH E14; msec; Tmax; PK; MTD

The ICH E14/S7B Questions and Answers (Q&As) guideline introduces the concept of a “double negative” nonclinical scenario (negative hERG assay and negative in vivo QTc study) to demonstrate that a drug does not produce a clinically relevant QT prolongation (i.e., no QT liability). This nonclinic...