Pharmacokinetics, Safety, and Tolerability of the Novel Chymase Inhibitor BAY 1142524 in Healthy Male Volunteers.

The orally available chymase inhibitor BAY 1142524 is currently being developed as a first‐in‐class treatment for left‐ventricular dysfunction after myocardial infarction. Results from 3 randomized, single‐center, phase 1 studies in healthy male volunteers examining the safety, tolerability, and pharmacokinetics of BAY 1142524 are summarized. In this first‐in‐human study, single oral doses of 1‐200 mg were administered in fasted state as liquid service formulation or immediate release (IR) tablets. The relative bioavailability and the effect of a high‐fat/high‐calorie meal were investigated at the 5‐mg dose. In a multiple‐dose escalation study, doses of 5‐50 mg twice daily and 100 mg once daily were given for 5 consecutive days. BAY 1142524 was safe and well tolerated and had no effects on heart rate or blood pressure compared with placebo. BAY 1142524 was absorbed with peak concentration 1‐3 hours after administration for IR tablets; it was eliminated from plasma with a terminal half‐life of 6.84‐12.0 hours after administration of liquid service formulation or IR tablets. Plasma exposures appeared to be dose‐linear, with a negligible food effect. There was only low accumulation of BAY 1142524 after multiple dosing. BAY 1142524 exhibited a pharmacokinetic profile allowing for once‐daily dosing. The absence of blood pressure effects after administration of BAY 1142524 supports the combination of this novel anti‐remodeling drug with existing standard of care in patients with left‐ventricular dysfunction after acute myocardial infarction. [ABSTRACT FROM AUTHOR]