title: Effects of K-877, a novel selective PPARα modulator (SPPARMα), in dyslipidaemic patients: A randomized, double blind, active- and placebo-controlled, phase 2 trial.
abstract: 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.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, Jichi Medical University, 3311-1, Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan. Electronic address: ishibash@jichi.ac.jp.
authors.forename: Shun
authors.initials: S
authors.lastname: Ishibashi
authors.affiliation: 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. Electronic address: shizu@imed2.med.osaka-u.ac.jp.
authors.forename: Shizuya
authors.initials: S
authors.lastname: Yamashita
authors.affiliation: National Center for Geriatrics and Gerontology, 7-430 Morioka-cho, Obu, Aichi, 474-8511, Japan. Electronic address: harai@ncgg.go.jp.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Arai
authors.affiliation: Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan. Electronic address: earaki@gpo.kumamoto-u.ac.jp.
authors.forename: Eiichi
authors.initials: E
authors.lastname: Araki
authors.affiliation: Department of Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan. Electronic address: kyokote@faculty.chiba-u.jp.
authors.forename: Koutaro
authors.initials: K
authors.lastname: Yokote
authors.affiliation: Clinical Data Science Department, Kowa Company, Ltd., 4-14, Nihonbashi-honcho 3 chome, Chuo-ku, Tokyo, 103-8433, Japan. Electronic address: suganami@kowa.co.jp.
authors.forename: Hideki
authors.initials: H
authors.lastname: Suganami
authors.affiliation: Fondation coeur et arteres, 96, rue Nationale, 59000, Lille, France. Electronic address: jean-charles.fruchart@fondacoeur.com.
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Fruchart
authors.affiliation: Laboratory for Systems Biology and Medicine (LSBM), Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo, 153-8904, Japan. Electronic address: kodama@lsbm.org.
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Kodama
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001583:Benzoxazoles / Q000627:therapeutic use*; D002087:Butyrates / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000188:drug therapy; D008078:Cholesterol, LDL / Q000097:blood; D004311:Double-Blind Method; D050171:Dyslipidemias / Q000188:drug therapy*; D005260:Female; D011345:Fenofibrate / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D007564:Japan; D008075:Lipoproteins, HDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D047493:PPAR alpha / Q000819:agonists*; D061214:Patient Safety; D014280:Triglycerides / Q000097:blood
chemical_list: D001583:Benzoxazoles; D002087:Butyrates; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C000603947:K-877 compound; D008075:Lipoproteins, HDL; D047493:PPAR alpha; D014280:Triglycerides; D011345:Fenofibrate
keywords: Dyslipidaemia; HDL; K-877; Pemafibrate; SPPARMα; Triglyceride