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 2:1 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.

中文翻译：

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高胆固醇血症患者在大剂量阿托伐他汀背景治疗中补充补充低密度脂蛋白胆固醇和降低其药代动力学的过程中，加入苯甲酸（ETC-1002）：一项随机安慰剂对照试验。

背景

比马多酸是一种口服的，每日一次的一流药物，正在开发中，用于治疗高胆固醇血症。

客观的

这项研究的目的是评估低密度脂蛋白胆固醇（LDL-C）降低苯丙酸在稳定的高强度阿托伐他汀背景疗法中的作用，以及单独使用阿托伐他汀并与稳态两栖动物联合使用的多剂量血浆药代动力学酸。

方法

这是针对高胆固醇血症患者的2期研究（NCT02659397）。患者每天接受一次开放标签的阿托伐他汀80 mg治疗4周，然后在基线时以2：1随机分配，以接受双盲双歧酸180 mg（n = 45）或安慰剂（n = 23）加开放标签的阿托伐他汀80 mg持续4周。随机分组后4周评估疗效。在首次使用苯二酸之前和治疗2周后，分析了阿托伐他汀及其代谢物的稳态水平。

结果

用80毫克阿托伐他汀进行的4周稳定期筛选降低了LDL-C值约40％。安慰剂调整后的最小二乘均值表明，从基线到第29天，使用苯二甲酸的LDL-C降低率为22％（P  = .003）。对于总胆固醇（−10％; P  = .014），非高密度脂蛋白胆固醇（−13％; P  = .015），载脂蛋白B（−15％），使用苯甲酸对基线进行安慰剂调整后的减少量也显着; P  = .004）和高敏感性C反应蛋白（-44％; P  = .002）。在曲线下，对稳态阿托伐他汀和邻羟基阿托伐他汀面积的苯二甲酸影响的点估计值<30％，并且在临床上无意义。

结论

在稳定的大剂量阿托伐他汀疗法中添加180 mg比美多酸有效地降低高胆固醇血症患者的LDL-C，而不会引起临床上重要的阿托伐他汀暴露量增加。