ESP 15228 / Esperion Therap - LARVOL DELTA

Phase 1, Single- and Multiple-Ascending-Dose, Food-Effect, and East Asian Subject Studies to Assess the Pharmacokinetics, Safety, and Tolerability of Bempedoic Acid, a Selective Inhibitor of Adenosine Triphosphate Citrate Lyase. (PubMed, Clin Pharmacol Drug Dev) - "Circulating concentrations of the active metabolite ESP15228 were 18.0% of bempedoic acid concentrations on average. Mean estimates of bempedoic acid elimination half-life in Japanese (25.2 hours) and Chinese (20.0 hours) subjects were comparable to Western subjects (23.9 hours) following 14 days of once-daily dosing. Bempedoic acid was generally safe and well tolerated up to a dose of 220 mg/day across the study populations described herein."

Journal • P1 data • PK/PD data • Dyslipidemia

The Disposition and Metabolism of Bempedoic Acid, A Potent Inhibitor of ATP Citrate Lyase, In Healthy Human Subjects. (PubMed, Drug Metab Dispos) - "Pooled plasma samples were characterized by the presence of bempedoic acid, which accounted for 59.3% of total plasma radioactivity, ESP15228 (a reversible keto metabolite of bempedoic acid), and their respective glucuronide conjugates. Significance Statement This study characterizes the disposition and metabolism of bempedoic acid, an inhibitor of ATP citrate lyase for hypercholesterolemia. This work provides further understanding of bempedoic acid clinical pharmacokinetics and clearance pathways in adult subjects."

Journal • Dyslipidemia • Metabolic Disorders

[VIRTUAL] Pharmacokinetics, Pharmacodynamics and Safety of Bempedoic Acid in a Phase 1 Clinical Trial in Healthy Japanese, Chinese and White Subjects (AHA 2021) - "Active metabolite ESP15228 AUC exposures were approximately 20% of BA across subjects. Results from this study suggest that administration of BA 180 mg once daily over 14 days markedly reduced LDL-C and was well tolerated in all subjects. PK differences, largely explained after normalizing CL/F and Vz/F by subject BW, are not expected to result in clinically meaningful differences in the efficacy or safety profiles of BA."

Clinical • P1 data • PK/PD data • CRP