PII-106 - COMPARATIVE PHARMACOKINETICS AND SAFETY OF DWJ1451 AND CO-ADMINISTRATION OF OLMESARTAN MEDOXOMIL/AMLODIPINE/ROSUVASTATIN AND EZETIMIBE TABLETS IN HEALTHY KOREAN SUBJECTS

S. Kim¹, N. Ha¹, S. Moon², M. Kim²; ¹Jeonbuk National University, ²Jeonbuk National University Medical School.

Background: A fixed-dose combination (FDC) of olmesartan medoxomil/amlodipine/rosuvastatin and ezetimibe was developed to improve medication compliance in patients with both hyper-tension and dyslipidemia. This study aimed to compare the pharmacokinetics and safety profiles of DWJ1451 (olmesartan medoxomil/amlodipine/rosuvastatin/ezetimibe FDC) and co-administration of one tablet of olmesartan medoxomil/amlodipine and one tablet of rosuvastatin/ezetimibe in healthy Korean subjects.

Methods: This study was designed as a randomized, open-label, single dose, 2-treatment, 2-period, 2-sequence, crossover study in healthy subjects. A total of 64 subjects were randomly as-signed to 1 of 2 sequences and received either the test drug DWJ1451 (one FDC tablet of olmesartan medoxomil 20 mg/amlodipine 5 mg/rosuvastatin 10 mg/ezetimibe 10 mg) or reference drug (one tablet of olmesartan medoxomil 20 mg/amlodipine 5 mg and one tab-let of rosuvastatin 10 mg/ezetimibe 10 mg) in each period with a 14-day washout. Blood samples were collected up to 72 hours post-dose for amlodipine and total ezetimibe, and 48 hours post-dose for olmesartan and rosuvastatin. Safety assessments were performed.

Results: Fifty-five subjects were included in the pharmacokinetic analysis for olmesartan and rosuvastatin, respectively, and 54 subjects were included in the pharmacokinetic analysis for amlodipine and total ezetimibe, respectively. The 90% confidence intervals for geo-metric mean ratios (test/reference) of AUClast and Cmax for olmesartan were 0.9812 (0.9460-1.0178) and 1.0046 (0.9638-1.0472), respectively; for amlodipine, the values were 0.9924 (0.9620-1.0237) and 0.9813 (0.9498-1.0138), respectively; for rosuvastatin, the values were 0.9524 (0.9078-0.9992) and 0.9407 (0.8796-1.0061), respectively; for total ezetimibe, the values were 0.9681 (0.9106-1.0293) and 0.8687 (0.8042-0.9383), re-spectively. There was no serious adverse event, and all reported adverse events were mild or moderate.

Conclusion: DWJ1451 showed comparable pharmacokinetic profiles to those of co-administration of separate tablets (one tablet of olmesartan medoxomil 20 mg/amlodipine 5 mg and one tab-let of rosuvastatin 10 mg/ezetimibe 10 mg). Both treatments were well tolerated and safe.