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The α2C‐adrenoreceptor antagonist BAY 1193397 is in development for the oral treatment of diabetic foot ulcers. Safety, tolerability, and pharmacokinetics of BAY 1193397 were investigated in 3 randomized, single‐center phase 1 studies in healthy male subjects: a first‐in‐human study (single oral doses of 0.5‐50 mg), a relative bioavailability and food effect study (single doses of 1 and 10 mg), and a multiple‐dose escalation study (using 2 and 5 mg twice daily and 10 and 20 mg once daily for 9 consecutive days). BAY 1193397 was rapidly absorbed in the fasted state, peak concentrations were reached between 0.6 and 2 hours. The mean terminal half‐life was in the range of 17 to 20 hours. Area under the plasma concentration–time curve and maximum concentration appeared to be dose proportional, with a negligible food effect. There were no high‐accumulation effects of BAY 1193397 after repeated dosing. BAY 1193397 was safe and well tolerated. At supratherapeutic plasma concentrations, there were slight transient increases in norepinephrine levels, heart rate, and blood pressure that were more pronounced after a single dose compared to steady state and appeared to be maximum concentration dependent. The results of the presented studies support the conduct of subsequent clinical trials with BAY 1193397 in patients with diabetes and compromised microcirculation. [ABSTRACT FROM AUTHOR]

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]