Active Ingredient: SONIDEGIB
A pooled pharmacokinetics/ECG analysis was conducted across 4 patient trials (341 oncology patients) and 4 healthy volunteer studies (204 subjects), including a dedicated steady-state sub-study of 62 patients. Matched PK-ECG data analyzed via a linear mixed-effect model showed that the mean change from baseline in Fridericia-corrected QT (ΔQTcF) at steady-state plasma concentrations for both the 200 mg therapeutic and 800 mg supratherapeutic doses remained strictly under 5 ms. The highest mean steady-state ΔQTcF was 2.7 ms (2 hours post-dose in the 800 mg cohort). The upper one-sided 95% confidence intervals were consistently below the 10-ms clinical threshold at all time points. No concentration-dependent QTc prolongation, ventricular arrhythmias, or Torsades de Pointes were reported.
https://doi.org/10.1007/s00228-016-2128-8