PII-091 - A PHASE 1 OPEN-LABEL, FIXED-SEQUENCE 3-PERIOD STUDY TO EVALUATE PHARMACOKINETIC INTERACTIONS BETWEEN FIMASARTAN AND INDAPAMIDE IN HEALTHY VOLUNTEERS

W. Shin¹, A. Yang², H. Yoo², A. Kim²; ¹1Department of Clinical Pharmacology and Therapeutics, CHA Bundang Medical Center, CHA Univer-sity School of Medicine, Seongnam, Gyeonggi-do, Republic of Korea, ²CHA Bundang Medical Center.

Background: Fimasartan (angiotensin II receptor antagonist) and indapamide (thiazide-like diuretics) have been expected as potential combination therapy for essential hypertension patients who do not adequately respond. This study aimed to evaluate the pharmacokinetic (PK) interactions and safety between fimasartan and indapamide.

Methods: This was an open-label, fixed-sequence, 3-period, drug-drug interaction phase 1 study to evaluate the PKs interactions between fimasartan and indapamide on steady-state, as follows: fimasartan 60mg once daily for five days (Period 1); after a 9-day washout period, indapamide sustained release (SR) 1.5 mg once daily for 5 days (Period 2); after a 2-day washout period, fimasartan 60 mg and indapamide SR 1.5 mg for five days (Period 3). A non-compartmental analysis was used to estimate the PK parameters. The exposures of fimasartan and indapamide at steady-state were compared to assess PKs interactions. Safety evaluations were conducted using laboratory tests, vital signs, physical examinations, 12-lead electrocardiograms (ECG), and treatment-emergent adverse events (TEAEs).

Results: A total of 31 subjects and 28 subjects were included in the safety analysis set and in the PK analysis set, respectively. For fimasartan, the geometric mean ratio (GMR) [90% confidence intervals, CI] for maximum concentration of drug in plasma at steady state (Cmax,ss), and area under the concentration-time profile during the dosing interval at steady state (AUCτ,ss) of co-administration to fimasartan alone were 1.1844 (0.8886–1.5787), and 1.2023 (1.1027–1.3109), respectively. For indapamide, GMR (90% CI) for Cmax,ss and AUCτ,ss of co-administration to indapamide alone were 0.9901 (0.8921–1.0988), and 0.9447 (0.8456–1.0556), respectively. There were no significant differences in the incidence of TEAE among the treatments. Except for TEAEs, no clinically significant changes in laboratory tests, vital signs, physical examinations, or ECG were observed in this study.

Conclusion: There is no clinically significant effects of drug interactions between fimasartan and indapamide on PK and safety profiles. These results provide the scientific basis to ensure the combination therapy of fimasartan and indapamide without concerns of drug interactions on PKs and safety.