108: Pharmacokinetic Comparison of Ezetimibe/Rosuvastatin/Telmisartan Fixed-dose Combination vs Coadministration of Separate Treatments

Statement of Purpose, Innovation or Hypothesis: Although combination therapy for hypertension and concurrent dyslipidemia is often required, low adherence due to polypharmacy can lead to treatment failure. Using fixed-dose combination (FDC) can increase adherence while providing equivalent therapeutic effect. To this end, this study aimed to evaluate the pharmacokinetics (PKs) for FDC of ezetimibe 10 mg/rosuvastatin 20 mg/telmisartan 80 mg (test) compared to separate tablets of ezetimibe 10 mg/rosuvastatin 20 mg FDC and telmisartan 80 mg (reference).

Description of Methods & Materials: 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 reference or test drug in each period. PK samples were collected up to 72 hours, and PK samples at the 3^rd and 4^th period were only collected for telmisartan to evaluate intrasubject variability. PK parameters of free ezetimibe, total ezetimibe, telmisartan, and rosuvastatin were calculated by noncompartmental analysis. Geometric mean ratios (GMRs) of PK parameters and their 90% confidence intervals (CIs) were calculated with linear mixed effect model between each treatment group. Routine safety evaluations including monitoring adverse events were performed.

Data & Results: 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 peak plasma concentration (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. Intrasubject coefficients of variation of C_max of reference treatment of telmisartan was 41.7%. All drug-related treatment-emergent adverse events were mild in severity and recovered without sequelae.

Interpretation, Conclusion or Significance: A fixed-dose combination of ezetimibe 10 mg/rosuvastatin 20 mg/telmisartan 80 mg demonstrated comparable pharmacokinetic and safety profiles to corresponding separate tablets.

Disclosures: This study was sponsored by Addpharma Pharmaceutical Corp., Korea. The authors do not have any conflicts of interest in this study.

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