Open AccessConcentration–QT Modeling Following Inhalation of the Novel Inhaled Phosphodiesterase‐4 Inhibitor CHF6001 in Healthy Volunteers Shows an Absence of QT Prolongation
Author(s) -
Jolling Koen,
Äbelö Angela,
Luyckx Nicolas,
Nandeuil MarieAnna,
Govoni Mirco,
Cella Massimo,
Lindauer Andreas
Publication year - 2019
Publication title -
cpt: pharmacometrics and systems pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.53
H-Index - 37
ISSN - 2163-8306
DOI - 10.1002/psp4.12405
Subject(s) - qt interval , medicine , phosphodiesterase , confidence interval , crossover study , inhalation , anesthesia , pharmacology , chemistry , biochemistry , alternative medicine , pathology , enzyme , placebo
Concentration‐ QT cF data obtained from two phase I studies in healthy volunteers treated with a novel phosphodiesterase‐4 inhibitor currently under development for the treatment of chronic obstructive pulmonary disease were analyzed by means of mixed‐effects modeling. A simple linear mixed‐effects model and a more complex model that included oscillatory functions were employed and compared. The slope of the concentration‐ QT cF relationship was not significantly greater than 0 in both approaches, and the simulations showed that the upper limit of the 90% confidence interval around the mean ΔΔ QT cF is not expected to exceed 10 ms within the range of clinically relevant concentrations. An additional simulation study confirmed the robustness of the simple linear mixed‐effects model for the analysis of concentration‐ QT data and supported the modeling of data obtained from studies with different designs (parallel and crossover).