S. Moon, D. Shin, I. Chung, S. Yi, H. Lee, I. Jang, K. Yu; Department of Clinical Pharmacology and Therapeutics, Seoul National University Hospital, Seoul, Korea, Republic of

BACKGROUND: LC23-1306, a reversible P2Y12 receptor antagonist, is under development for management of atherosclerotic disease. This study evaluated safety, pharmacokinetics (PK) and pharmacodynamics (PD) of LC23-1306.
METHODS: A randomized, double-blind, active and placebo-controlled, single and multiple ascending dose study was conducted in 108 healthy Korean subjects. Subjects were allocated to single-dose groups of 10, 30, 100, 200, 400, and 600 mg, and 7-day multiple oral dose groups of 100, 200, 400, and 600 mg. Ticagrelor 90 mg bid was used as active control in multiple dose study. Serial blood samples for PK/PD analysis were collected up to 48 h for single-dose and up to 72 h at steady state for multiple-dose. For PD evaluation, inhibition of platelet aggregation (IPA) was measured. Safety was assessed by adverse events (AEs), vital signs, ECG, and clinical laboratory tests.
RESULTS: Median time to peak concentration of LC23-1306 was observed at 1.5 - 4.0 h in all dose groups and was similar between single-dose and steady state. Maximum concentration (Cmax) and area under concentration-time curve (AUC) showed dose linearity from 100 to 600 mg, both after single dosing and at steady state. The accumulation index for LC23-1306 was 1.2 to 1.7. IPA became greater as dose increased, with maximum inhibition achieved at 2 h post-dose; IPA >50% was sustained up to 24 h (single) and 48 h (multiple) post-dose at doses of 200 to 600 mg. There were no serious AEs or clinically significant changes related to LC23-1306.
CONCLUSION: LC23-1306 was well tolerated in healthy subjects up to 600 mg single and multiple-dose without extensive accumulation. Systemic exposure showed dose linearity, and IPA was effective from 2 to 24 h in 200 - 600 mg cohorts; therefore, LC23-1306 can be given once daily as antiplatelet agent.