Efficacy and Safety of Pemafibrate (K-877), A selective Peroxisome Proliferator-activated Receptor α Modulator, in Patients with Dyslipidemia: Results from a 24-week, Randomized, Double Blind, Active-controlled, Phase 3 Trial

Background: To overcome the concerns associated with the use of fibrates, pemafibrate (K-877), a novel selective peroxisome proliferator-activated receptor modulator, was developed. In a previous phase 2 trial, we showed excellent efficacy and safety of pemafibrate in patients with dyslipidemia.

Objective: The objective of the study was to evaluate the efficacy and safety of pemafibrate over 24 weeks in adults with dyslipidemia in comparison with fenofibrate.

Methods: In this multicenter, 24-week, double-blind, clinical study, 225 patients with high triglyceride (TG; ≥150 mg/dL [1.7 mmol/L] and <500 mg/dL [5.7 mmol/L]) and relatively low high-density lipoprotein cholesterol (<50 mg/dL [1.3 mmol/L] in men or 55 mg/dL [1.4 mmol/L] in women) levels were randomized to receive either pemafibrate at 0.2 or 0.4 mg/d or fenofibrate 106.6 mg/d.

Results: Pemafibrate 0.2, 0.4 mg/d and fenofibrate significantly reduced TG levels from baseline by -46.2%, -45.9%, and -39.7%, respectively. As compared with fenofibrate, the least squares mean differences (95% confidence intervals) in TG were -6.5% (-12.0, -1.1) and -6.2% (-11.6, -0.8) in pemafibrate 0.2 and 0.4 mg/d respectively, which showed the superiority of these doses of pemafibrate to 106.6 mg/d of fenofibrate. The incidence rates of adverse drug reactions in pemafibrate groups (2.7% and 6.8%) were significantly lower than that in the fenofibrate group (23.7%). Pemafibrate significantly decreased alanine aminotransferase and gamma-glutamyltransferase levels, whereas fenofibrate increased both of them. The increments of serum creatinine and cystatin C were smaller in pemafibrate than those in fenofibrate.

Conclusions: Pemafibrate was superior to fenofibrate in terms of serum TG-lowering effect and hepatic and renal safety.