Abstract 427: An Oral, Rising, Multiple-dose Tolerance, Pharmacokinetic, and Pharmacodynamic Study of Gemcabene in Healthy Volunteers

Background: Gemcabene is a novel lipid-regulating compound being developed as an adjunct to diet and statin therapy for the treatment of dyslipidemia. Gemcabene was administered in a randomized, double-blind, rising, multiple-dose safety, tolerance, pharmacokinetic, and pharmacodynamic study in healthy subjects. Methods: Fifty healthy subjects (34 men and 16 women), with a mean age of 39.7 years and mean baseline LDL-C of 116.7 mg/dL were randomized (6:1) to either gemcabene 50, 150, 300, 450, 600/750, or 900 mg or placebo once daily for 29 days in six rising-dose cohorts. Results: Forty-seven subjects completed the study. Gemcabene significantly lowered total cholesterol by 18-21%, low-density lipoprotein-cholesterol (LDL-C) by 26-32%, and apolipoprotein B (apoB) by 8-21% from both baseline and placebo at the 450, 750/600, and 900 mg doses ( Table below ). Gemcabene was rapidly absorbed with dose proportional increases in maximum plasma concentration (Cmax) and area under plasma concentration time curve from 0 to 24 hours (AUC (0-24) ) values. Elimination half-life values were independent of dose and averaged 32-41 hours. Multiple doses of gemcabene up to 900 mg for 29 days were generally well-tolerated. There were no treatment-related serious adverse events. Adverse events reported were generally mild to moderate in intensity. Conclusion: Gemcabene exposure increased proportional with dose, was well tolerated, and was observed to significantly lower total cholesterol, LDL-C, and apo B at once daily doses of 450 to 900 mg. Gemcabene is being developed as an oral, lipid-altering agent to be used as an adjunctive therapy for the treatment of dyslipidemia, including the rare indication of HoFH. Clinical Implications: Gemcabene is being developed as a potential treatment for dyslipidemia.