Ishibashi Shun, Yamashita Shizuya, Arai Hidenori, Araki Eiichi, Yokote Koutaro, Suganami Hideki, Fruchart Jean-Charles, Kodama Tatsuhiko
Division of Endocrinology and Metabolism, Department of Medicine, Jichi Medical University, 3311-1, Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan.
Department of Community Medicine and Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan; Rinku General Medical Center, 2-23 Ourai-kita, Rinku, Izumisano, Osaka 598-8577, Japan.
Atherosclerosis. 2016 Jun;249:36-43. doi: 10.1016/j.atherosclerosis.2016.02.029. Epub 2016 Feb 26.
To assess the efficacy and safety of K-877 (Pemafibrate), a novel selective peroxisome proliferator-activated receptor α modulator (SPPARMα) that possesses unique PPARα activity and selectivity, compared with placebo and fenofibrate in dyslipidaemic patients with high triglyceride (TG) and low high-density lipoprotein cholesterol (HDL-C) levels.
This study was a double blind, placebo-controlled, parallel-group 12-week clinical trial. The study randomized 224 patients to K-877 0.025, 0.05, 0.1, 0.2 mg BID, fenofibrate 100 mg QD, or placebo (1:1:1:1:1:1) groups. Least squares mean percent changes from the baseline TG levels were -30.9%, -36.4%, -42.6%, -42.7% for the K-877 0.025, 0.05, 0.1, 0.2 mg BID respectively (p < 0.001), which were greater than that of the fenofibrate 100 mg QD (-29.7%, p < 0.001) group. Statistically significant improvements from the baseline HDL-C, very-low-density lipoprotein cholesterol, chylomicron cholesterol, remnant lipoprotein cholesterol, apolipoprotein (apo) B (apoB), and apoC-III were also observed in the K-877 groups. The incidence of adverse events (AEs) in the K-877 groups (32.4-56.8%) was comparable to those in placebo (47.2%) and fenofibrate 100 mg QD (56.8%); adverse drug reactions (ADRs) in the K-877 groups (2.7-5.4%) were less than those in placebo (8.3%) and fenofibrate 100 mg QD (10.8%) groups.
In dyslipidaemic patients with high TG and low HDL-C, K-877 improved TG, HDL-C, and other lipid parameters without increasing AEs or ADRs, compared to placebo and fenofibrate. K-877 can be expected to improve atherogenicity and to be a new beneficial treatment for dyslipidaemic patients.
评估新型选择性过氧化物酶体增殖物激活受体α调节剂（SPPARMα）K-877（匹伐贝特）与安慰剂及非诺贝特相比，在高甘油三酯（TG）和低高密度脂蛋白胆固醇（HDL-C）水平的血脂异常患者中的疗效和安全性，K-877具有独特的PPARα活性和选择性。
本研究为一项双盲、安慰剂对照、平行组12周的临床试验。该研究将224例患者随机分为K-877 0.025、0.05、0.1、0.2mg每日两次组、非诺贝特100mg每日一次组或安慰剂组（1:1:1:1:1:1）。K-877 0.025、0.05、0.1、0.2mg每日两次组从基线TG水平的最小二乘均值百分比变化分别为-30.9%、-36.4%、-42.6%、-42.7%（p<0.001），均高于非诺贝特100mg每日一次组（-29.7%，p<0.001）。在K-877组中，从基线HDL-C、极低密度脂蛋白胆固醇、乳糜微粒胆固醇、残粒脂蛋白胆固醇、载脂蛋白（apo）B（apoB）和apoC-III也观察到了具有统计学意义的改善。K-877组不良事件（AE）的发生率（32.4 - 56.8%）与安慰剂组（47.2%）和非诺贝特100mg每日一次组（56.8%）相当；K-877组药物不良反应（ADR）的发生率（2.7 - 5.4%）低于安慰剂组（8.3%）和非诺贝特100mg每日一次组（10.8%）。
在高TG和低HDL-C的血脂异常患者中，与安慰剂和非诺贝特相比，K-877改善了TG、HDL-C及其他血脂参数，且未增加AE或ADR。预计K-877可改善动脉粥样硬化性，是血脂异常患者一种新的有益治疗方法。
