Efficacy and Safety of K-877 (pemafibrate), a Selective PPARα Modulator, in European Patients on Statin Therapy

Background High plasma triglyceride (TG) is an independent risk factor for cardiovascular disease. Fibrates lower TG-levels through PPARα agonism. Currently available fibrates, however, have relatively low selectivity for PPARα. Objectives 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. 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-C ≤50 mg/dL for men and ≤55 mg/dL for women. Participants were randomized to receive placebo or one of 6 pemafibrate regimens: 0.05 mg BID, 0.1 mg BID, 0.2 mg BID, 0.1 mg QD, 0.2 mg QD, or 0.4 mg QD. The primary endpoints 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 BID 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-C levels, whereas apoB100 was unchanged. Pemafibrate was safe and well-tolerated, with only minor increases in serum creatinine and homocysteine concentrations. Conclusion Pemafibrate is effective, safe, and well-tolerated for the reduction of TG in European populations with hypertriglyceridemia despite statin treatment.