Efficacy and Safety of K-877 (Pemafibrate), a Selective PPARα Modulator, in European Patients on Statin Therapy
Jazyk angličtina Země Spojené státy americké Médium print
Typ dokumentu klinické zkoušky, fáze II, časopisecké články, randomizované kontrolované studie, práce podpořená grantem
PubMed
35238894
DOI
10.2337/dc21-1288
PII: 144603
Knihovny.cz E-zdroje
- MeSH
- benzoxazoly MeSH
- butyráty MeSH
- deriváty kyseliny fibrové terapeutické užití MeSH
- dospělí MeSH
- dvojitá slepá metoda MeSH
- hypertriglyceridemie * farmakoterapie MeSH
- lidé MeSH
- PPAR alfa metabolismus MeSH
- statiny * terapeutické užití MeSH
- triglyceridy MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze II MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
- Názvy látek
- (R)-2-(3-((benzoxazol-2-yl-d4 (3-(4-methoxyphenoxy-d7)propyl)amino)methyl)phenoxy) butanoic acid MeSH Prohlížeč
- benzoxazoly MeSH
- butyráty MeSH
- deriváty kyseliny fibrové MeSH
- PPAR alfa MeSH
- statiny * MeSH
- triglyceridy MeSH
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.
1st City Clinical Hospital named after E E Volosevitch Arkhangelsk Russia
Department of Medicine Vagelos College of Physicians and Surgeons Columbia University New York NY
Department of Vascular Medicine Amsterdam UMC Amsterdam the Netherlands
Hungarian Defense Forces Medical Centre Budapest Hungary
Citace poskytuje Crossref.org