PMID- 27062408 OWN - NLM STAT- MEDLINE DCOM- 20171120 LR - 20220331 IS - 1879-1484 (Electronic) IS - 0021-9150 (Linking) VI - 249 DP - 2016 Jun TI - Effects of K-877, a novel selective PPARalpha modulator (SPPARMalpha), in dyslipidaemic patients: A randomized, double blind, active- and placebo-controlled, phase 2 trial. PG - 36-43 LID - S0021-9150(16)30072-7 [pii] LID - 10.1016/j.atherosclerosis.2016.02.029 [doi] AB - BACKGROUND AND AIMS: To assess the efficacy and safety of K-877 (Pemafibrate), a novel selective peroxisome proliferator-activated receptor alpha modulator (SPPARMalpha) that possesses unique PPARalpha 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 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. 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. CI - Copyright (c) 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved. FAU - Ishibashi, Shun AU - Ishibashi S AD - 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. FAU - Yamashita, Shizuya AU - Yamashita S AD - 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. FAU - Arai, Hidenori AU - Arai H AD - National Center for Geriatrics and Gerontology, 7-430 Morioka-cho, Obu, Aichi, 474-8511, Japan. Electronic address: harai@ncgg.go.jp. FAU - Araki, Eiichi AU - Araki E AD - 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. FAU - Yokote, Koutaro AU - Yokote K AD - 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. FAU - Suganami, Hideki AU - Suganami H AD - 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. FAU - Fruchart, Jean-Charles AU - Fruchart JC AD - Fondation coeur et arteres, 96, rue Nationale, 59000, Lille, France. Electronic address: jean-charles.fruchart@fondacoeur.com. FAU - Kodama, Tatsuhiko AU - Kodama T AD - 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. CN - K-877-04 Study Group LA - eng PT - Clinical Trial, Phase II PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20160226 PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 RN - 0 (Benzoxazoles) RN - 0 (Butyrates) RN - 0 (Cholesterol, LDL) RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) RN - 0 (K-877 compound) RN - 0 (Lipoproteins, HDL) RN - 0 (PPAR alpha) RN - 0 (Triglycerides) RN - U202363UOS (Fenofibrate) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Benzoxazoles/*therapeutic use MH - Butyrates/*therapeutic use MH - Cardiovascular Diseases/drug therapy MH - Cholesterol, LDL/blood MH - Double-Blind Method MH - Dyslipidemias/*drug therapy MH - Female MH - Fenofibrate/therapeutic use MH - Humans MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use MH - Japan MH - Lipoproteins, HDL/blood MH - Male MH - Middle Aged MH - PPAR alpha/*agonists MH - Patient Safety MH - Triglycerides/blood OTO - NOTNLM OT - Dyslipidaemia OT - HDL OT - K-877 OT - Pemafibrate OT - SPPARMalpha OT - Triglyceride EDAT- 2016/04/12 06:00 MHDA- 2017/11/29 06:00 CRDT- 2016/04/11 06:00 PHST- 2016/02/03 00:00 [received] PHST- 2016/02/24 00:00 [accepted] PHST- 2016/04/11 06:00 [entrez] PHST- 2016/04/12 06:00 [pubmed] PHST- 2017/11/29 06:00 [medline] AID - S0021-9150(16)30072-7 [pii] AID - 10.1016/j.atherosclerosis.2016.02.029 [doi] PST - ppublish SO - Atherosclerosis. 2016 Jun;249:36-43. doi: 10.1016/j.atherosclerosis.2016.02.029. Epub 2016 Feb 26.