The Journal of antimicrobial chemotherapy
No clinically relevant QTc prolongation with ceftibuten or ledaborbactam etzadroxil: concentration-QTc analyses from two phase I studies
Par Darpo B, Xue H, Hamed KA et 4 autres.
Contenu en anglais
Résumé
Objective
Ceftibuten and ledaborbactam etzadroxil are being developed as an oral fixed-dose combination for the treatment of complicated urinary tract infections caused by multidrug-resistant Enterobacterales. This study evaluated their effects on cardiac repolarization using concentration-QTc analyses.
Methods
ECG and pharmacokinetic data from two randomized, single-centre, double-blind, placebo-controlled, phase I, dose-escalation studies in healthy adults (ClinicalTrials.gov: NCT04314206 and NCT04243863) were analysed using concentration-QTc modelling. Thirty-six participants were randomized to the ceftibuten study (27 active, nine placebo) and 48 to the ledaborbactam etzadroxil study (36 active, 12 placebo). Linear mixed-effects models characterized the relationship between plasma concentrations and placebo-corrected change from baseline in Fridericia-corrected QT interval (ΔΔQTcF). Model-based predictions estimated QTc effects across observed and clinically relevant plasma concentrations.