Abstract 13981: Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Profile of Multiple-Doses of DRL-17822, a Potent Cholesteryl Ester Transfer Protein Inhibitor in Healthy Male Subjects
Hypothesis and Introduction: The inhibition of cholesteryl ester transfer protein (CETP) is considered as a potential new mechanism for treatment of dyslipidemia. DRL-17822 is an orally active, potent and specific CETP inhibitor currently in development for the treatment of dyslipidemia, atherosclerosis and associated cardiovascular disease. DRL-17822 was well tolerated in single doses up to 1000 mg and showed dose dependent CETP inhibition.
Methods: Safety, tolerability, pharmacokinetics and pharmacodynamics were evaluated in a randomized, double-blind, placebo controlled study in healthy male subjects with HDL-C levels ≤ 1.3 mmol/L. Four groups of 8 subjects each were treated under fed conditions with DRL-17822 50, 150, 300 or 450 mg or placebo, once daily for 14 days.
Results: DRL-17822 was well tolerated. There were no serious adverse events. All adverse events were mild in nature. There were no clinically meaningful changes in blood pressure, or ECG. There were no clinically meaningful changes in laboratory parameters including adrenal hormones (aldosterone and cortisol). Steady state was reached after 4 to 6 days of dosing and the terminal half-life ranged from 100 to 140 hours. Trough CETP inhibition ranged from 40% to 100%. Statistically significant increases in HDL-C (51% to 111%) and decreases in LDL-C (−25% to −56%) were observed at all dose levels of DRL-17822 compared to placebo at day 15.
Conclusion: Pharmacologic activity of DRL 17822 has been demonstrated by inhibition of CETP activity, increase in HDL-C levels and decrease in LDL-C levels in healthy subjects. DRL-17822 was well tolerated at all doses without meaningful changes in blood pressure, ECG or laboratory parameters including adrenal hormones.
- © 2010 by American Heart Association, Inc.