Complementary low-density lipoprotein-cholesterol lowering and pharmacokinetics of adding bempedoic acid (ETC-1002) to high-dose atorvastatin background therapy in hypercholesterolemic patients: A randomized placebo-controlled trial.
J Clin Lipidol
; 13(4): 568-579, 2019.
Article
en En
| MEDLINE
| ID: mdl-31202641
ABSTRACT
BACKGROUND:
Bempedoic acid is an oral, once-daily, first-in-class medication being developed to treat hypercholesterolemia.OBJECTIVE:
The aim of the study was to assess the low-density lipoprotein cholesterol (LDL-C)-lowering efficacy of bempedoic acid added to stable high-intensity atorvastatin background therapy and multiple-dose plasma pharmacokinetics of atorvastatin alone and combined with steady-state bempedoic acid.METHODS:
This was a phase 2 study in patients with hypercholesterolemia (NCT02659397). Patients received once-daily open-label atorvastatin 80 mg for 4 weeks then were randomized 21 at baseline to receive double-blind bempedoic acid 180 mg (n = 45) or placebo (n = 23) plus open-label atorvastatin 80 mg for 4 weeks. Efficacy was assessed 4 weeks after randomization. Atorvastatin and metabolites' steady-state levels were analyzed before first dosing with bempedoic acid and after 2 weeks of treatment.RESULTS:
The 4-week stabilization phase with 80 mg atorvastatin resulted in approximately 40% lowering of LDL-C values from screening. The placebo-adjusted least squares mean lowering of LDL-C from baseline to Day 29 with bempedoic acid was 22% (P = .003). Placebo-adjusted reductions from baseline with bempedoic acid also were significant for total cholesterol (-10%; P = .014), non-high-density lipoprotein cholesterol (-13%; P = .015), apolipoprotein B (-15%; P = .004), and high-sensitivity C-reactive protein (-44%; P = .002). Point estimates of bempedoic acid effects on steady-state atorvastatin and ortho-hydroxy atorvastatin area under the curve were <30% and not clinically meaningful.CONCLUSIONS:
Bempedoic acid 180 mg added to stable high-dose atorvastatin therapy effectively lowers LDL-C in patients with hypercholesterolemia without causing clinically important increases in atorvastatin exposure.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Ácidos Dicarboxílicos
/
Ácidos Grasos
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Hipercolesterolemia
/
Anticolesterolemiantes
Tipo de estudio:
Clinical_trials
/
Prognostic_studies
Límite:
Aged
/
Humans
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Male
/
Middle aged
Idioma:
En
Revista:
J Clin Lipidol
Asunto de la revista:
BIOQUIMICA
/
METABOLISMO
Año:
2019
Tipo del documento:
Article