Abstract 529: Long-Term Efficacy and Safety Profile of Ezetimibe 10 mg in the Treatment of Patients with Homozygous Sitosterolemia: A Multi-center, Open-Label, 2-Year Extension Study
Objective: Assess the long-term efficacy/safety profile of ezetimibe (EZE) 10 mg/day in patients with homozygous sitosterolemia (HoS).
Methods: This was an extension of a multi-center, randomized, double-blind, placebo-controlled base study in which patients with HoS and plasma sitosterol levels > 5 mg/dL were randomized 4:1 to EZE 10 mg/day (n = 30) or placebo (n = 7) for 8 wks. Patients who successfully completed the base study with > 80% compliance to study medication were eligible to enter two, successive 1-year extension studies in which open-label EZE 10 mg/day was administered. Patients remained on their current treatment regimen (e.g. bile salt binding resin, statin and low sterol diet) during the base and extension studies. Patients were off base study drug for ≥4 wks prior to entering the first extension. Efficacy and safety/tolerability parameters were evaluated every 12 and 24 wks in the first and second years, respectively. The primary efficacy endpoint was mean % change in plasma sitosterol from baseline to study end for the cohort of patients (n = 21) who successfully completed the second extension.
Results: EZE 10 mg/day led to significant reductions from baseline in plasma levels of sitosterol, campesterol, LDL-Sterol, total sterol, and apo B (see Table⇓). No significant changes from baseline were observed for lathosterol, high-density lipoprotein sterols, triglycerides, or apo A-1. Maximal reductions in plasma levels of sitosterol and campesterol occurred in the first 28 and 52 wks, respectively, and remained stable thereafter. Maximal reductions in LDL-S were achieved by Wk 4 and were maintained throughout the duration of the extension study. A small, non-significant reduction in Achilles tendon thickness was observed at 2 years. Overall EZE 10 mg was well tolerated.
Conclusion: In patients with HoS, treatment with EZE 10 mg/day for 2 years effectively reduced plasma plant sterol concentrations with an overall favorable safety profile.