First-in-human single dose study of the CETP inhibitor BAY 60-5521 shows dose-dependent CETP inhibition and HDL rise (Br J Clin Pharmacol 2012)

Original title: Single dose pharmacokinetics, pharmacodynamics, tolerability and safety of BAY 60-5521, a potent inhibitor of cholesteryl ester transfer protein

Br J Clin Pharmacol · 1 February 2012 · 6

Boettcher MF, Heinig R, Schmeck C, Kohlsdorfer C, Ludwig M, Schaefer A, Gelfert-Peukert S, Wensing G, Weber O

In a randomised, single-blind, placebo-controlled, single dose-escalation first-in-man study, thirty-eight healthy young men received oral BAY 60-5521, a potent CETP inhibitor, at 5, 12.5, 25 or 50 mg or placebo. Only one drug-related adverse event occurred across all doses (mild skin rash at 25 mg), with no clinically relevant laboratory changes and no effects on heart rate, blood pressure or ECG. Clear dose-dependent CETP inhibition was seen from 5 mg, with inhibition exceeding 50% for 18 hours at 25 mg and for more than 50 hours at 50 mg, and mean HDL cholesterol rose about 30% relative to baseline after 50 mg, with a terminal half-life of 76 to 144 hours, demonstrating BAY 60-5521 was safe, well tolerated and pharmacodynamically active.

Original abstract

Aims: To determine pharmacokinetics (PK), pharmacodynamics (PD), tolerability and safety of BAY 60-5521, a potent inhibitor of cholesteryl ester transfer protein (CETP).

Methods: The first in man (FIM) study investigated the safety, tolerability, pharmacodynamics and pharmacokinetics in healthy male subjects following administration of single oral doses. The study was performed using a randomized, single-blind, placebo-controlled, single dose-escalation design. Thirty-eight young healthy male subjects (aged 20-45 years) received an oral dose of 5, 12.5, 25 or 50 mg BAY 60-5521 (n= 28) or were treated with a placebo (n= 10).

Results: In all four dose steps, only one adverse event (25 mg; mild skin rash) was considered drug related. Clinical laboratory parameters showed no clinically relevant changes. A clear dose-dependent CETP inhibition could be demonstrated starting at a dose of 5 mg. At a dose of 25 mg, a CETP inhibition >50% over 18 h was observed. After 50 mg, CETP inhibition >50% lasted more than 50 h. Twenty-four h after administration mean HDL-C-values showed a nearly dose-proportional increase. Following administration of 50 mg, a significant HDL-C increase of about 30% relative to baseline values was found. BAY 60-5521 was slowly absorbed reaching maximum concentrations in plasma after 4 to 6 h. The disposition in plasma was multi-exponential with an estimated mean terminal half-life of 76 to 144 h.

Conclusions: BAY 60-5521 was clinically safe and well tolerated. No effects on heart rate, blood pressure and ECG recordings were observed during the study. A clear pharmacodynamic effect on CETP inhibition and HDL could be demonstrated.

Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.