Effects of K-877, a novel selective PPARα modulator (SPPARMα), in dyslipidaemic patients: A randomized, double blind, active- and placebo-controlled, phase 2 trial

Shun Ishibashi, Shizuya Yamashita, Hidenori Arai, Eiichi Araki, Koutaro Yokote, Hideki Suganami, Jean-Charles Fruchart, Tatsuhiko Kodama
2016 Atherosclerosis  
Background and aims: To assess the efficacy and safety of K-877 (Pemafibrate), a novel selective peroxisome proliferator-activated receptor a modulator (SPPARMa) that possesses unique PPARa activity and selectivity, compared with placebo and fenofibrate in dyslipidaemic patients with high triglyceride (TG) and low high-density lipoprotein cholesterol (HDL-C) levels. Methods and results: This study was a double blind, placebo-controlled, parallel-group 12-week clinical trial. The study
more » ... 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 À30.9%, À36.4%, À42.6%, À42.7% 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 (À29.7%, 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 (32.4e56.8%) was comparable to those in placebo (47.2%) and fenofibrate 100 mg QD (56.8%); adverse drug reactions (ADRs) in the K-877 groups (2.7e5.4%) were less than those in placebo (8.3%) and fenofibrate 100 mg QD (10.8%) groups. Conclusion: 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.
doi:10.1016/j.atherosclerosis.2016.02.029 pmid:27062408 fatcat:jstsen5tfjaylczwifeqouapoy