Evaluation of the Effects of CHF6001, an Inhaled PDE4 Inhibitor, on Cardiac Repolarization and Cardiac Arrhythmias in Healthy Volunteers

Abstract

Chronic obstructive pulmonary disease (COPD) is a multicomponent condition characterized by airway inflammation and associated to comorbidities, including cardiovascular diseases. Among anti-inflammatory agents in development for COPD, the phosphodiesterase inhibitors administrated by inhalation have the potential for increased efficacy and reduced systemic side effects. CHF6001 is an inhaled PDE4 inhibitor with proven anti-inflammatory properties in animal models. This randomized, double-blind, placebo-controlled study was aimed to demonstrate its cardiovascular safety and tolerability in healthy male volunteers with normal electrocardiogram and cardiac parameters. Single and multiple ascending doses (7 days of administration) of CHF6001 were administered. Three electrocardiograms were recorded at several pharmacokinetic time points and at each time points, postdose heart rate, QRS and PR intervals, and presence of arrhythmia were evaluated. In single ascending dose, QTcF intervals did not increase more than 30 milliseconds from the baseline, all heart rate was between 45 and 100 bpm, and no statistically significant differences were observed in PR and QRS intervals. In multiple ascending dose, cardiac parameters did not differ significantly from baseline. In the pharmacokinetic/pharmacodynamic analysis, no medically or clinically significant changes were found. Further studies are ongoing to demonstrate that CHF6001 is safe and well tolerated in COPD patients as well.

Tanimilast, A Novel Inhaled Pde4 Inhibitor for the Treatment of Asthma and Chronic Obstructive Pulmonary Disease

“…An in-depth evaluation of the effects of tanimilast on cardiac repolarization and cardiac arrhythmias was conducted in healthy volunteers using repeated 24-h electrocardiogram recordings from the FIH and FIH EXTENSION studies ( Table 3 ). The global cardiac safety profile of tanimilast showed the absence of potential meaningful QTc liability as well as PR and QRS prolongation or change in heart rate or cardiac arrhythmia counts ( Ferrari et al, 2016 ). In particular, concentration–QT data were analyzed by means of mixed-effects modelling ( Jolling et al, 2019 ).…”