Efficacy and safety of K-877, a novel selective peroxisome proliferator-activated receptor α modulator (SPPARMα), in combination with statin treatment: Two randomised, double-blind, placebo-controlled clinical trials in patients with dyslipidaemia

Autor: Hideki Suganami, Koutaro Yokote, Hidenori Arai, Eiichi Araki, Shun Ishibashi, Shizuya Yamashita
Rok vydání: 2016
Předmět:
Adult
Male
medicine.medical_specialty
Statin
Time Factors
Combination therapy
medicine.drug_class
Peroxisome proliferator-activated receptor
030204 cardiovascular system & hematology
Pharmacology
Placebo
Gastroenterology
03 medical and health sciences
chemistry.chemical_compound
Young Adult
0302 clinical medicine
Double-Blind Method
Japan
Internal medicine
medicine
Humans
PPAR alpha
030212 general & internal medicine
Pitavastatin
Triglycerides
Aged
Hypolipidemic Agents
chemistry.chemical_classification
Hypertriglyceridemia
Benzoxazoles
Triglyceride
business.industry
Middle Aged
Residual risk
Clinical trial
Butyrates
Treatment Outcome
chemistry
Quinolines
Drug Therapy
Combination
Female
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Cardiology and Cardiovascular Medicine
business
Biomarkers
medicine.drug
Signal Transduction
Zdroj: Atherosclerosis. 261
ISSN: 1879-1484
Popis: Substantial residual cardiovascular risks remain despite intensive statin treatment. Residual risks with high triglyceride and low high-density lipoprotein cholesterol are not the primary targets of statins. K-877 (pemafibrate) demonstrated robust efficacy on triglycerides and high-density lipoprotein cholesterol and a good safety profile as a monotherapy. The aim of these studies was to evaluate the efficacy and safety of K-877 add-on therapy to treat residual hypertriglyceridaemia during statin treatment.The objectives were investigated in two, multicentre, randomised, double-blind, placebo-controlled, parallel group comparison clinical trials: (A) K-877 0.1, 0.2, and 0.4 mg/day in combination with pitavastatin for 12 weeks in 188 patients, (B) K-877 0.2 (fixed dose) and 0.2 (0.4) (conditional up-titration) mg/day in combination with any statin for 24 weeks in 423 patients.In both studies, we found a robust reduction in fasting triglyceride levels by approximately 50% in all combination therapy groups, which was significant compared to the statin-monotherapy (placebo) groups (p 0.001). High-performance liquid chromatography analysis for lipoprotein subfractions revealed that atherogenic lipoprotein profiles were ameliorated by K-877 add-on therapy, i.e. small low-density lipoproteins decreased whereas larger ones increased, and larger high-density lipoproteins decreased whereas smaller ones increased. The incidence rates of adverse events and adverse drug reactions in K-877 combination therapy groups were comparable to those in statin-monotherapy groups without any noteworthy event in both studies.These results strongly support the favourable benefit-to-risk ratio of K-877 add-on therapy in combination with statin treatment.
Databáze: OpenAIRE
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