TY - JOUR
T1 - Efficacy and Safety of K-877 (Pemafibrate), a Selective PPARα Modulator, in European Patients on Statin Therapy
AU - Ginsberg, Henry N.
AU - Hounslow, Neil J.
AU - Senko, Yusuke
AU - Suganami, Hideki
AU - Bogdanski, Pawel
AU - Ceska, Richard
AU - Kalina, Akos
AU - Libis, Roman A.
AU - Supryadkina, Tatiana V.
AU - Hovingh, G. Kees
N1 - Funding Information: The authors thank the investigators and patients who participated in this study and Prof. John Kastelein for advice on the design of the trial. The trial was supported by Faisal Zaman (project manager), Alastair Sword (statistician), and Ursula Schlichtiger (medical monitor) from Medpace Europe. Laboratory tests were conducted by Medpace Reference Laboratories (Leuven, Bel-gium), and ion mobility analyses were per-formed by UCSF Benioff Children’s Hospital (Oakland, CA). Medical writing support, funded by Kowa Company Ltd., was provided by Jackie Read, PhD, of GK Pharmacomm Ltd. Funding. This study was sponsored by Kowa Research Europe, Ltd., an affiliate of Kowa Company, Ltd., Tokyo, Japan. Funding Information: The trial was sponsored by Kowa Research Europe, Ltd. The study proto col was approved by the Independent Central/National Ethics Committee and local ethics committees if applicable, and Clinical Trial Authorization was granted by competent authorities for each center. The study was conducted according to the Declaration of Helsinki and the principles of Good Clinical Practice. Written informed consent was obtained from all participants. Publisher Copyright: © 2022, American Diabetes Association Inc.. All rights reserved.
PY - 2022/4/1
Y1 - 2022/4/1
N2 - OBJECTIVE: High plasma triglyceride (TG) is an independent risk factor for cardiovascular disease. Fibrates lower TG levels through peroxisome proliferator-activated receptor α (PPARα) agonism. Currently available fibrates, however, have relatively low selectivity for PPARα. The aim of this trial was to assess the safety, tolerability, and efficacy of K-877 (pemafibrate), a selective PPARα modulator, in statin-treated European patients with hypertriglyceridemia. RESEARCH DESIGN AND METHODS: A total of 408 statin-treated adults were recruited from 68 European sites for this phase 2, randomized, double-blind, placebo-controlled trial. They had fasting TG between 175 and 500 mg/dL and HDL-cholesterol (HDL-C) ≤50 mg/dL for men and ≤55 mg/dL for women. Participants were randomly assigned to receive placebo or one of six pemafibrate regimens: 0.05 mg twice a day, 0.1 mg twice a day, 0.2 mg twice a day, 0.1 mg once daily, 0.2 mg once daily, or 0.4 mg once daily. The primary end points were TG and non-HDL-C level lowering at week 12. RESULTS: Pemafibrate reduced TG at all doses (adjusted P value <0.001), with the greatest placebo-corrected reduction from baseline to week 12 observed in the 0.2-mg twice a day treatment group (54.4%). Reductions in non-HDL-C did not reach statistical significance. Reductions in TG were associated with improvements in other markers for TG-rich lipoprotein metabolism, including reductions in apoB48, apoCIII, and remnant cholesterol and an increase in HDL-C levels. Pemafibrate increased LDL-cholesterol levels, whereas apoB100 was unchanged. Pemafibrate was safe and well-tolerated, with only minor increases in serum creatinine and homocysteine concentrations. CONCLUSIONS: Pemafibrate is effective, safe, and well-tolerated for the reduction of TG in European populations with hypertriglyceridemia despite statin treatment.
AB - OBJECTIVE: High plasma triglyceride (TG) is an independent risk factor for cardiovascular disease. Fibrates lower TG levels through peroxisome proliferator-activated receptor α (PPARα) agonism. Currently available fibrates, however, have relatively low selectivity for PPARα. The aim of this trial was to assess the safety, tolerability, and efficacy of K-877 (pemafibrate), a selective PPARα modulator, in statin-treated European patients with hypertriglyceridemia. RESEARCH DESIGN AND METHODS: A total of 408 statin-treated adults were recruited from 68 European sites for this phase 2, randomized, double-blind, placebo-controlled trial. They had fasting TG between 175 and 500 mg/dL and HDL-cholesterol (HDL-C) ≤50 mg/dL for men and ≤55 mg/dL for women. Participants were randomly assigned to receive placebo or one of six pemafibrate regimens: 0.05 mg twice a day, 0.1 mg twice a day, 0.2 mg twice a day, 0.1 mg once daily, 0.2 mg once daily, or 0.4 mg once daily. The primary end points were TG and non-HDL-C level lowering at week 12. RESULTS: Pemafibrate reduced TG at all doses (adjusted P value <0.001), with the greatest placebo-corrected reduction from baseline to week 12 observed in the 0.2-mg twice a day treatment group (54.4%). Reductions in non-HDL-C did not reach statistical significance. Reductions in TG were associated with improvements in other markers for TG-rich lipoprotein metabolism, including reductions in apoB48, apoCIII, and remnant cholesterol and an increase in HDL-C levels. Pemafibrate increased LDL-cholesterol levels, whereas apoB100 was unchanged. Pemafibrate was safe and well-tolerated, with only minor increases in serum creatinine and homocysteine concentrations. CONCLUSIONS: Pemafibrate is effective, safe, and well-tolerated for the reduction of TG in European populations with hypertriglyceridemia despite statin treatment.
UR - http://www.scopus.com/inward/record.url?scp=85128159973&partnerID=8YFLogxK
U2 - https://doi.org/10.2337/dc21-1288
DO - https://doi.org/10.2337/dc21-1288
M3 - Article
C2 - 35238894
SN - 0149-5992
VL - 45
SP - 898
EP - 908
JO - Diabetes Care
JF - Diabetes Care
IS - 4
ER -