An Open-label, Randomized, Single-dose, Crossover Study in Healthy Adult Volunteers to Evaluate Pharmacokinetic Interactions and Tolerability of a Fixed-dose Combination with Rosuvastatin and Ezetimibe

Recent studies have shown that adding ezetimibe to statins could further reduce levels of Low-Density Lipoprotein Cholesterol (LDL-C), total cholesterol and triglycerides, and likely increase high-density lipoprotein cholesterol levels. We conducted an open-label, crossover, single-dose, 3 periods study in 34 healthy Mexican volunteers under fasting conditions, randomly allocated into 3 treatment groups: Rosuvastatin (20 mg), ezetimibe (10 mg), and FDC of rosuvastatin (20 mg) and ezetimibe (10 mg), to evaluate the pharmacokinetics (PKs) of drug interactions between rosuvastatin and ezetimibe as well as the tolerability of the Fixed-Dose Combination (FDC). All subjects were administered the FDC tablet as well as the same dose of both drugs given separately as monotherapy. The geometric mean ratio (90% CI) for rosuvastatin in FDC over the single dose was 1.032 (0.937-1.138) for Cmax and 1.09 (0.998-1.190) for AUC0-inf. In the case of ezetimibe Cmax was 0.897 (0.829-0.971) with an AUC0-inf of 0.993 (0.916-1.076). A total of 8 Adverse Events (AEs) were reported, the frequency was similar for FDC than in the treatments administered separately. No clinically significant PK interactions between rosuvastatin and ezetimibe were found, studied parameters were within conventionally accepted bioequivalence criteria. Tolerability profiles showed to be similar; therefore, the FDC was well tolerated.