PII-014 - PHARMACOKINETIC DRUG INTERACTION BETWEEN FEXUPRAZAN (DWP14012), A NOVEL POTASSIUM-COMPETITIVE ACID BLOCKER, AND NON-STEROIDAL ANTI-INFLAMMATORY DRUGS IN HEALTHY SUBJECTS.

H. Won¹, J. Na¹, H. Song², S. Kim², J. Oh¹, I. Jang¹; ¹Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea, ²Daewoong Pharmaceutical Co., Ltd., Seoul, Republic of Korea.

Background: Anti-acid agents are commonly used for prevention of non-steroidal anti-inflammatory drugs (NSAIDs) induced peptic ulcers, and fexuprazan (DWP14012), a novel potassium-competitive acid blocker, is expected to prevent NSAID-induced ulcer. This study aimed to evaluate pharmacokinetic (PK) interactions between fexuprazan and NSAIDs.

Methods: A randomized, open-label, 2-period, fixed-sequence study was conducted in healthy male subjects. Subjects randomly received one of the study drugs (fexuprazan 40 mg BID, celecoxib 200 mg BID, naproxen 500 mg BID, or meloxicam 15 mg QD) for 5 or 7 days in the first period followed by combination of fexuprazan and one of NSAIDs in the second period. Serial blood samples were collected until 48- or 72-hour post-dose at steady-state for PK analysis. PK parameters including area under plasma concentration-time curve over dosing interval at steady state (AUCtau,ss) and maximum plasma concentration at steady state (Cmax,ss) were compared between monotherapy and combination therapy.

Results: A total of 103 subjects completed the study. PK interactions between fexuprazan and NSAIDs were not clinically significant. Geometric mean ratios (GMRs) and 90% confidence intervals (CIs) of combination to monotherapy for AUCtau,ss and Cmax,ss were within 0.8-1.25 except for one case. When fexuprazan was administered with naproxen, the AUCtau,ss and Cmax,ss of fexuprazan were increased about 20%, but those were not regarded as clinically meaningful changes considering previously reported exposure-response relationship and safety profile of fexuprazan.

Conclusion: There were no clinically significant PK interactions between fexuprazan and NSAIDs. It supports the co-administration of fexuprazan and NSAIDs for prevention NSAID-induced peptic ulcer.