Long-Term Effects of Extended-Release Pemafibrate Tablets on Dyslipidemia and Safety in Triglyceridemic Patients: A Phase 3, Multicenter, Randomized, Open-Label, Parallel-Group Study

<bold>Aims:</bold> Long-term safety and efficacy of pemafibrate once-daily extended-release (XR) tablets, taken in morning or evening, were evaluated in dyslipidemic patients with high triglycerides (TG). <bold>Methods:</bold> In this multicenter, randomized, open-label, parallel-group, phase 3 long-term study, dyslipidemic patients with high TG were randomly assigned to morning or evening administration of XR for 52 weeks. The dose was started at 0.2 mg/day and increased to 0.4 mg/day for patients having fasting serum TG >= 150mg/dL during treatment. The primary efficacy endpoint was percent change in fasting serum TG. <bold>Results:</bold> The study enrolled 121 patients, assigning 61 to morning and 60 to evening administration. The study population included 71.1% males. Mean age was 58.5 +/- 11.1 (mean +/- SD) years, body mass index 27.7 +/- 4.3 kg/m(2), and fasting TG 264.0 +/- 109.2 mg/dL. Fasting serum TG decreased significantly from baseline to 52 weeks among patients overall and in the morning and evening groups (-45.7%, -44.8%, and -46.6%, respectively, p < 0.001 vs. baseline). The difference in least-squares mean between the morning and evening groups was 3.0%, not statistically significant. The dose was increased in 82 patients (44 morning and 38 evening), with 57.3% (95%CI 45.9, 68.2) achieving fasting serum TG < 150 mg/dL. Adverse events occurred in 83.5% and adverse drug reactions in 19.0% but with no notable safety problems. <bold>Conclusions:</bold> Long-term, once-daily administration of XR was effective and safe in dyslipidemic patients with high TG. XR provided favorable TG-lowering effects regardless of morning or evening administration, and the XR dose increase proved effective in patients having initially inadequate response.