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
•Pemafibrate 0.2 to 0.4 mg/d was superior to fenofibrate 106.6 mg/d in triglyceride lowering.•Pemafibrate decreased total cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B, while it increased high-density lipoprotein and apolipoprotein AI.•Adverse drug reactions were significantly fewer in pemafibrate groups.•Liver- and kidney-related adverse effects were fewer in pemafibrate groups.•Pemafibrate significantly decreased fibrinogen compared with fenofibrate. BackgroundTo 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.ObjectiveThe objective of the study was to evaluate the efficacy and safety of pemafibrate over 24 weeks in adults with dyslipidemia in comparison with fenofibrate.MethodsIn 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.ResultsPemafibrate 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.ConclusionsPemafibrate was superior to fenofibrate in terms of serum TG-lowering effect and hepatic and renal safety. 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. 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. 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. 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. Pemafibrate was superior to fenofibrate in terms of serum TG-lowering effect and hepatic and renal safety.