Pharmacokinetic comparison of ezetimibe/rosuvastatin/telmisartan 10/20/80 mg fixed-dose combination versus coadministration of separate tablets in healthy participants

Abstract This study aimed to evaluate the pharmacokinetics (PKs) for fixed-dose combination (FDC) of ezetimibe/rosuvastatin/telmisartan 10/20/80 mg (test) compared to separate tablets of ezetimibe/rosuvastatin 10/20 mg FDC and telmisartan 80 mg (reference). A randomized, open-label, 4-period, 2-sequence replicated crossover study was conducted in healthy participants. Each treatment group received a single oral dose of test or reference drug in each period. PK samples during the 1st and 2nd periods were collected for all three drugs, while only telmisartan concentration was measured in the 3rd and 4th periods to evaluate intra-subject variability (ISV) of telmisartan. Geometric mean ratios (GMRs) of PK parameters and their 90% confidence intervals (CIs) were calculated with a linear mixed effect model between each treatment group. To account for the high ISV of telmisartan’s peak plasma concentration ( C max ), the scaled average bioequivalence (SABE) approach was considered in this analysis. A total of 58 participants were randomized, and 49 participants completed the study. PK profiles were comparable between treatments. The GMR and 90% CIs (test-to-reference) of area under the time-concentration curve and C max were 0.9835 (0.9260–1.0446) and 0.9873 (0.8830–1.1039) for free ezetimibe, and 0.9937 (0.9459–1.0440) and 1.0617 (0.9844–1.1415) for total ezetimibe. For rosuvastatin, corresponding values were 0.9465 (0.8883–1.0086) and 0.9062 (0.8135–1.0096); for telmisartan, 0.9728 (0.9315–1.0159) and 0.9724 (0.8846–1.0690), respectively. The result established equivalence without utilizing the SABE approach, although the ISV of telmisartan’s C max was 40.7%. A FDC of ezetimibe/rosuvastatin/telmisartan 10/20/80 mg demonstrated comparable pharmacokinetic profiles to corresponding separate treatments.